Cyclooxygenase‐2 modulates cellular growth and promotes tumorigenesis

O C Trifan; T Hla

doi:10.1111/j.1582-4934.2003.tb00222.x

. 2007 May 1;7(3):207–222. doi: 10.1111/j.1582-4934.2003.tb00222.x

Cyclooxygenase‐2 modulates cellular growth and promotes tumorigenesis

O C Trifan ^1,^✉, T Hla ¹

PMCID: PMC6741314 PMID: 14594546

Abstract

Cyclooxygenase (COX)‐2 and the prostaglandins resulting from its enzymatic activity have been shown to play a role in modulating cell growth and development of human neoplasia. Evidence includes a direct relationship between COX‐2 expression and cancer incidence in humans and animal models, increased tumorigenesis after genetic manipulation of COX‐2, and significant anti‐tumor properties of non‐steroidal anti‐inflammatory drugs in animal models and in some human cancers. Recent data showed that COX‐2 and the derived prostaglandins are involved in control of cellular growth, apoptosis, and signal through a group of nuclear receptors named peroxisome proliferator‐activated receptors (PPARs). In this article we will review some of the findings suggesting that COX‐2 is involved in multiple cellular mechanisms that lead to tumorigenesis.

Keywords: Cyclooxygenase‐1 and‐2, prostaglandins, cell growth, tumorigenesis, nonsteroidal anti‐inflammatory drugs, angiogenesis, apoptosis, peroxisome proliferator‐activated receptors

References

1. Smith W.L., The eicosanoids and their biochemical mechanisms of action, Biochem. J., 259: 315–324, 1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
2. Hla T. Ristimaki A., Appleby S., Barriocanal J. G., Cyclooxygenase gene expression in inflammation and angiogenesis, Ann. N. Y. Acad. Sci., 696: 197–204, 1993. [DOI] [PubMed] [Google Scholar]
3. Schror K., The effect of prostaglandins and thromboxane A2 on coronary vessel tone‐mechanisms of action and therapeutic implications, Eur. Heart. J., 14(Suppl I): 34–41, 1993. [PubMed] [Google Scholar]
4. Davies P., Bailey P.J., Goldenberg M.M., Ford‐Hutchinson A.W., The role of arachidonic acid oxygenation products in pain and inflammation, Annu. Rev. Immunol., 2: 335–357, 1984. [DOI] [PubMed] [Google Scholar]
5. Vane J.R., Botting R.M., Anti‐inflammatory drugs and their mechanism of action, Inflamm. Res., 47(Suppl 2): S78–S87, 1998. [DOI] [PubMed] [Google Scholar]
6. Futaki N., Takahashi S., Yokoyama M., Arai I., Higuchi S., Otomo S., NS‐398, a new anti‐inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX‐2) activity in vitro , Prostaglandins, 47: 55–59, 1994. [DOI] [PubMed] [Google Scholar]
7. Smith C.J., Zhang Y., Koboldt C.M., Muhammad J., Zweifel B.S., Shaffer A., Talley J.J., Masferrer J.L., Seibert K., Isakson P.C., Pharmacological analysis of cyclooxygenase‐1 in inflammation, Proc. Natl. Acad. Sci. U.S.A., 95: 13313–13318, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
8. Chan C.C., Boyce S., Brideau C., Charleson S., Cromlish W., Ethier D., Evans J., Ford‐Hutchinson A.W., Forrest M.J., Gauthier J.Y., et al., Rofecoxib [Vioxx, MK‐0966; 4‐(4′‐methylsulfonylphenyl)‐3‐phenyl‐2‐(5H)‐furanone]: a potent and orally active cyclooxygenase‐2 inhibitor. Pharmacological and biochemical profiles, J. Pharmacol. Exp. Ther., 290: 551–560, 1999. [PubMed] [Google Scholar]
9. McAdam B.F., Catella‐Lawson F., Mardini I.A., Kapoor S., Lawson J.A., FitzGerald G.A., Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)‐2: the human pharmacology of a selective inhibitor of COX‐2, Proc. Natl. Acad. Sci. U.S.A., 96: 272–277, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
10. Smith W.L., DeWitt D.L., Prostaglandin endoperoxide H synthases‐1 and −2, Adv. Immunol., 62: 167–215, 1996. [DOI] [PubMed] [Google Scholar]
11. Sirois J., Simmons D.L., Richards J.S., Hormonal regulation of messenger ribonucleic acid encoding a novel isoform of prostaglandin endoperoxide H synthase in rat preovulatory follicles. Induction in vivo and in vitro, J. Biol. Chem., 267: 11586–11592, 1992. [PubMed] [Google Scholar]
12. O'Sullivan M.G., Chilton F.H., Huggins E.M. Jr, McCall C.E., Lipopolysaccharide priming of alveolar macrophages for enhanced synthesis of prostanoids involves induction of a novel prostaglandin H synthase, J. Biol. Chem., 267: 14547–14550, 1992. [PubMed] [Google Scholar]
13. Evett G.E., Xie W., Chipman J.G., Robertson D.L., Simmons D.L., Prostaglandin G/H synthase isoenzyme 2 expression in fibroblasts: regulation by dexamethasone, mitogens, and oncogenes, Arch. Biochem. Biophys., 306: 169–177, 1993. [DOI] [PubMed] [Google Scholar]
14. DeWitt D.L., Meade E.A., Serum and glucocorticoid regulation of gene transcription and expression of the prostaglandin H synthase‐1 and prostaglandin H synthase‐2 isozymes, Arch. Biochem. Biophys., 306: 94–102, 1993. [DOI] [PubMed] [Google Scholar]
15. Jones D.A., Carlton D.P., McIntyre T.M., Zimmerman G.A., Prescott S.M., Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines, J. Biol. Chem., 268: 9049–9054, 1993. [PubMed] [Google Scholar]
16. Smith W. L., Garavito R. M., DeWitt D. L., Prostaglandin endoperoxide H synthase (Cyclooxygenases)‐1 and −2, J. Biol. Chem., 271: 33157–33160, 1996. [DOI] [PubMed] [Google Scholar]
17. Simon L.S., Role and regulation of cyclooxygenase‐2 during inflammation, Am. J. Med., 106: 37S–42S, 1999. [DOI] [PubMed] [Google Scholar]
18. Hla T., Neilson K., Human cyclooxygenase‐2 cDNA, Proc. Natl. Acad. Sci. USA, 89: 7384–7388, 1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
19. Kraemer S. A., Meade E. A., DeWitt D. L., Prostaglandin endoperoxide synthase gene structure: identification of the transcriptional start site and 5′‐flanking regulatory sequences, Arch. Biochem. Biophys., 293: 391–400, 1992. [DOI] [PubMed] [Google Scholar]
20. Kujubu D. A., Herschman H. R., Dexamethasone inhibits mitogen induction of the TIS10 prostaglandin synthase/cyclooxygenase gene, J. Biol. Chem., 267: 7991–7994, 1992. [PubMed] [Google Scholar]
21. Reddy S.T., Herschman H. R., Prostaglandin synthase‐1 and prostaglandin synthase‐2 are coupled to distinct phospholipases for the generation of prostaglandin D2 in activated mast cells, J. Biol. Chem., 272: 3231–3237, 1997. [DOI] [PubMed] [Google Scholar]
22. Devchand P. R., Keller H., Peters J. M., Vazquez M., Gonzalez F. J., Wahli W., The PPARalpha‐leukotriene B4 pathway to inflammation control, Nature, 384: 39–43, 1996. [DOI] [PubMed] [Google Scholar]
23. Forman B. M., Tontonoz P., Chen J., Brun R. P., Spiegelman B. M., Evans R. M., 15‐Deoxy‐delta 12, 14‐prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma, Cell, 83: 803–812, 1995. [DOI] [PubMed] [Google Scholar]
24. Morita I., Schindler M., Regier M.K., Otto J.C., Hori T., DeWitt D.L., Smith W.L., Different intracellular locations for prostaglandin endoperoxide H synthase‐1 and −2, J. Biol. Chem., 270: 10902–10908, 1995. [DOI] [PubMed] [Google Scholar]
25. Spencer A. G., Woods J. W., Arakawa T., Singer I. I., Smith W. L., Subbcellular localization of Prostaglandin endoperoxide H synthase‐1 and −2 by immunoelectron microscopy, J.Biol. Chem., 273: 9886–9893, 1998. [DOI] [PubMed] [Google Scholar]
26. Tontonoz P., Hu E., Spiegelman B. M., Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid activated transcription factor, Cell, 79: 1147–1156, 1994. [DOI] [PubMed] [Google Scholar]
27. Howe L.R., Subbaramaiah K., Chung W.J., Dannenberg A.J., Brown A.M., Transcriptional activation of cyclooxygenase‐2 in Wnt‐1‐transformed mouse mammary epithelial cells, Cancer Res., 59: 1572–1577, 1999. [PubMed] [Google Scholar]
28. Roman C.D., Morrow J., Whitehead R., Beauchamp R.D., Induction of cyclooxygenase‐2 and invasiveness by transforming growth factor‐beta(1) in immortalized mouse colonocytes expressing oncogenic Ras, J. Gastrointest. Surg., 6: 304–309, 2002. [DOI] [PubMed] [Google Scholar]
29. Sheng, H. , Williams, C. S. , Shao, J. , Liang, P. , DuBois, R. N. , Beauchamp, R. D. , Induction of cyclooxygenase‐2 by activated Ha‐ras oncogene in Rat‐1 fibroblasts and the role of mitogen‐activated protein kinase pathway, J. Biol. Chem., 273: 22120–22127, 1998. [DOI] [PubMed] [Google Scholar]
30. Sheng, G. G. , Shao, J. , Sheng, H. , Hooton, E. B. , Isakson, P. C. , Morrow, J. D. , Coffey, R. J. , DuBois, R. N. , Beauchamp, R. D. , A selective cyclooxygenase 2 inhibitor suppresses the growth of H‐ras‐transformed rat intestinal epithelial cells, Gastroenterology, 113: 1883–1891, 1997. [DOI] [PubMed] [Google Scholar]
31. Subbaramaiah, K. , Telang, N. , Ramonetti, J. T. , Araki, R. , DeVito, B. , Weksler, B. B. , Dannenberg, A. J. , Transcription of cyclooxygenase‐2 is enhanced in transformed mammary epithelial cells, Cancer Res., 56: 4424–4429, 1996. [PubMed] [Google Scholar]
32. Heasley, L. E. , Thaler, S. , Nicks, M. , Price, B. , Skorecki, K. , Nemenoff, R. A. , Induction of cytosolic phospholipase A2 by oncogenic Ras in human non‐small cell lung cancer, J. Biol. Chem., 272, 14501–14504, 1997. [DOI] [PubMed] [Google Scholar]
33. Ristimaki A., Garfinkel S., Wessendorf J., Maciag T., Hla T., Induction of cyclooxygenase‐2 by interleukin‐1 alpha. Evidence for post‐transcriptional regulation, J. Biol. Chem., 269: 11769–11775, 1994. [PubMed] [Google Scholar]
34. Yamamoto K., Arakawa T., Ueda N., Yamamoto S., Transcriptional roles of nuclear factor kappa B and nuclear factor‐interleukin‐6 in the tumor necrosis factor alphadependent induction of cyclooxygenase‐2 in MC3T3‐E1 cells, J. Biol. Chem., 270: 31315–31320, 1995. [DOI] [PubMed] [Google Scholar]
35. Liu S.F., Ye X., Malik A.B., Inhibition of NF‐kappaB activation by pyrrolidine dithiocarbamate prevents in vivo expression of proinflammatory genes, Circulation, 100: 1330–1337, 1999. [DOI] [PubMed] [Google Scholar]
36. Matsuura H., Sakaue M., Subbaramaiah K., Kamitani H., Eling T.E., Dannenberg A.J., Tanabe T., Inoue H., Arata J., Jetten A.M., Regulation of cyclooxygenase‐2 by interferon gamma and transforming growth factor alpha in normal human epidermal keratinocytes and squamous carcinoma cells, J. Biol. Chem., 274: 29138–29148, 1999. [DOI] [PubMed] [Google Scholar]
37. Nakagawa T., Fujita N., Oh‐Hara T., Kurokawa T., Nakamura K., Tsuruo T., Interleukin‐1 alpha induced cyclooxygenase‐2 expression in bone‐derived endothelial cells, J. Cell. Physiol., 179: 226–232, 1999. [DOI] [PubMed] [Google Scholar]
38. Kage K., Fujita N., Oh‐hara T., Ogata E., Fujita T., Tsuruo T., Basic fibroblast growth factor induces cyclooxygenase‐2 expression in endothelial cells derived from bone, Biochem. Biophys. Res. Commun., 254: 259–263, 1999. [DOI] [PubMed] [Google Scholar]
39. Kirtikara K., Laulederkind S. J., Raghow R., Kanekura T., Ballou L. R., An accessory role for ceramide in interleukin‐1beta induced prostaglandin synthesis, Mol. Cell. Biochem., 181: 41–48, 1998. [DOI] [PubMed] [Google Scholar]
40. Blanco A., Habib A., Levy‐Toledano S., Maclouf J., Involvement of tyrosine kinases in the induction of cyclooxygenase‐2 in human endothelial cells, Biochem. J., 312: 419–423, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
41. Kennelly P.J., Krebs E.G., Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases, J. Biol. Chem., 266: 15555–15558, 1991. [PubMed] [Google Scholar]
42. Vezza R., Habib A., Li H., Lawson J. A., FitzGerald G.A., Regulation of cyclooxygenases by protein kinase C. Evidence against the importance of direct enzyme phosphorylation, J. Biol. Chem., 271: 30028–30033, 1996. [DOI] [PubMed] [Google Scholar]
43. Schmedtje J. F. Jr., Ji Y‐S., Liu W. ‐L., DuBois R. N., Runge S. M., Hypoxia induces cyclooxygenase‐2 via the NF‐kB p65 transcription factor in human vascular endothelial cells, J. Biol. Chem., 272: 601–608, 1997. [DOI] [PubMed] [Google Scholar]
44. Shweiki D., Itin A., Soffer D., Keshet E., Vascular endothelial growth factor induced by hypoxia may mediate hypoxia‐initiated angiogenesis, Nature 359: 843–845, 1992. [DOI] [PubMed] [Google Scholar]
45. Levy G. N., Prostaglandin H synthases, nonsteroidal antiinflammatory drugs, and colon cancer, FASEB J., 11: 234–247, 1997. [PubMed] [Google Scholar]
46. Rosenberg L., Louik C., Shapiro S., Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma, Cancer 82: 2326–2333, 1998. [DOI] [PubMed] [Google Scholar]
47. Giardiello. F.M. , Offerhaus. G.J. , DuBois. R.N. , The role of nonsteroidal anti‐inflammatory drugs in colorectal cancer prevention, Eur. J. Cancer, 31A: 1071–1076, 1995. [DOI] [PubMed] [Google Scholar]
48. Reddy B.S., Maruyama H., Kelloff G., Dose‐related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal antiinflammatory drug, during different stages of rat colon tumor development, Cancer Res., 47: 5340–5346, 1987. [PubMed] [Google Scholar]
49. Masferrer J.L., Leahy K.M., Koki A.T., Zweifel B.S., Settle S.L., Woerner B.M., Edwards D.A., Flickinger A.G., Moore R.J., Seibert K., Antiangiogenic and antitumor activities of cyclooxygenase‐2 inhibitors, Cancer Res., 60: 1306–11, 2000. [PubMed] [Google Scholar]
50. Trifan O.C., Durham W.F., Salazar V., Horton J., Levine B.D., Zweifel B.S., Davis T.W., Masferrer J.L., COX‐2 inhibition with celecoxib enhances anti‐tumor efficacy and reduces diarrhea side effect of CPT‐11, Cancer Res., 62: 5778–5784, 2002. [PubMed] [Google Scholar]
51. Zweifel B.S., Davis T.W., Ornberg R.L., Masferrer J.L., Direct evidence for a role of cyclooxygenase 2‐derived prostaglandin E2 in human head and neck xenograft tumors, Cancer Res., 62: 6706–6711, 2002. [PubMed] [Google Scholar]
52. Peterson H.I., Effects of prostaglandin synthesis inhibitors on tumor growth and vascularization. Experimental studies in the rat, Invasion Metastasis, 3: 151–159, 1983. [PubMed] [Google Scholar]
53. Tsujii M., Kawano S., Tsuji S., Sawaoka H., Hori M., DuBois R.N., Cyclooxygenase regulates angiogenesis induced by colon cancer cells, Cell 93: 705–716, 1998. [DOI] [PubMed] [Google Scholar]
54. Chu J., Lloyd F.L., Trifan O.C., Knapp B., Rizzo M.T., Potential involvement of the cyclooxygenase‐2 pathway in the regulation of tumor‐associated angiogenesis and growth in pancreatic cancer, Mol. Cancer Ther., 2: 1–7, 2003. [PubMed] [Google Scholar]
55. Majima M., Isono M., Ikeda Y., Hayashi I., Hatanaka K., Harada Y., Katsumata O., Yamashina S., Katori M., Yamamoto S., Significant roles of inducible cyclooxygenase (COX)‐2 in angiogenesis in rat sponge implants, Jpn. J. Pharmacol., 75: 105–114, 1997. [DOI] [PubMed] [Google Scholar]
56. Daniel T.O., Liu H., Morrow J.D., Crews B.C., Marnett L.J., Thromboxane A2 is a mediator of cyclooxygenase‐2‐dependent endothelial migration and angiogenesis, Cancer Res., 59: 4574–4577, 1999. [PubMed] [Google Scholar]
57. Sawaoka H., Tsuji S., Tsujii M., Gunawan E.S., Sasaki Y., Kawano S., Hori M., Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo, Lab. Invest., 79: 1469–77, 1999. [PubMed] [Google Scholar]
58. Masferrer J.L., Koki A., Seibert K., COX‐2 inhibitors. A new class of antiangiogenic agents, Ann. N. Y. Acad. Sci., 889: 84–68, 1999. [DOI] [PubMed] [Google Scholar]
59. Yamada M., Kawai M., Kawai Y., Mashima Y., The effect of selective cyclooxygenase‐2 inhibitor on corneal angiogenesis in the rat, Curr. Eye Res., 19: 300–304, 1999. [DOI] [PubMed] [Google Scholar]
60. Qiao L., Shiff S.J., Rigas B., Sulindac sulfide inhibits the proliferation of colon cancer cells: diminished expression of the proliferation markers PCNA and Ki‐67, Cancer Lett., 115, 229–234, 1997. [DOI] [PubMed] [Google Scholar]
61. Zhang X., Morham S.G., Langenbach R., Young D.A., Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase‐null embryo fibroblasts, J. Exp. Med., 190, 451–459, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
62. Hara A., Yoshimi N., Niwa M., Ino N., Mori H., Apoptosis induced by NS‐398, a selective cyclooxygenase‐2 inhibitor, in human colorectal cancer cell lines, Jpn. J. Cancer Res., 88: 600–604, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
63. Ding X.Z., Tong W.G., Adrian T.E., Blockade of cyclooxygenase‐2 inhibits proliferation and induces apoptosis in human pancreatic cancer cells, Anticancer Res., 20: 2625–31, 2000. [PubMed] [Google Scholar]
64. Hida T., Kozaki K., Muramatsu H., Masuda A., Shimizu S., Mitsudomi T., Sugiura T., Ogawa M., Takahashi T., Cyclooxygenase‐2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non‐small cell lung cancer cell lines, Clin. Cancer Res., 6: 2006–2011, 2000. [PubMed] [Google Scholar]
65. Hanif R., Pittas A., Feng Y., Koutsos M.I., Qiao L., Staiano‐Coico L., Shiff S.I., Rigas B., Effects of nonsteroidal anti‐inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin‐independent pathway, Biochem. Pharmacol., 52: 237–245, 1996. [DOI] [PubMed] [Google Scholar]
66. Elder D.J., Hague A., Hicks D.J., Paraskeva C., Different growth inhibition by the aspirin metabolite salicylate in human colorectal tumor cell lines: enhanced apoptosis in carcinoma and in vitro transformed adenoma relative to adenoma cell lines, Cancer Res., 56: 2273–2276, 1996. [PubMed] [Google Scholar]
67. Grosch S., Tegeder I., Niederberger E., Brautigam L., Geisslinger G., COX‐2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX‐2 inhibitor celecoxib, FASEB J., 15: 2742–2744, 2001. [DOI] [PubMed] [Google Scholar]
68. Richter M., Weiss M., Weinberger I., Furstenberger G., Marian B., Growth inhibition and induction of apoptosis in colorectal tumor cells by cyclooxygenase inhibitors, Carcinogenesis, 22: 17–25, 2001. [DOI] [PubMed] [Google Scholar]
69. Rigas B., Shiff S.J., Is inhibition of cyclooxygenase required for the chemopreventive effect of NSAIDs in colon cancer A model reconciling the current contradiction, Med. Hypotheses, 54: 210–5, 2000. [DOI] [PubMed] [Google Scholar]
70. Hsu A.L., Ching T.T., Wang D.S., Song X., Rangnekar V.M., Chen C.S., The cyclooxygenase‐2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl‐2, J. Biol. Chem., 275: 11397–11403, 2000. [DOI] [PubMed] [Google Scholar]
71. Grilli M., Pizzi M., Memo M., Spano P., Neuroprotection by aspirin and sodium salicylate through blockade of NF‐kappaB activation, Science, 274: 1383–1385, 1996. [DOI] [PubMed] [Google Scholar]
72. Yin M.J., Yamamoto Y., Gaynor R.B., The anti‐inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase‐beta, Nature, 396: 77–78, 1998. [DOI] [PubMed] [Google Scholar]
73. Yamamoto Y., Yin M.J., Lin K.M., Gaynor R.B., Sulindac inhibits activation of the NF‐kappaB pathway, J. Biol. Chem., 274: 27307–27314, 1999. [DOI] [PubMed] [Google Scholar]
74. Stark L.A., Din F.V., Zwacka R.M., Dunlop M.G., Aspirin‐induced activation of the NF‐kappaB signaling pathway: a novel mechanism for aspirin‐mediated apoptosis in colon cancer cells, FASEB J., 15: 1273–1275, 2001. [PubMed] [Google Scholar]
75. Chan T.A., Morin P.J., Vogelstein B., Kinzler K.W., Mechanisms underlying nonsteroidal antiinflammatory drug‐mediated apoptosis, Proc. Natl. Acad. Sci. U.S.A., 95: 681–686, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
76. He T.C., Chan T.A., Vogelstein B., Kinzler K.W., PPARdelta is an APC‐regulated target of nonsteroidal antiinflammatory drugs, Cell, 99: 335–345, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
77. Jaradat M.S., Wongsud B., Phornchirasilp S., Rangwala S.M., Shams G., Sutton M., Romstedt K.J., Noonan D.J., Feller D.R., Activation of peroxisome proliferator‐activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin, Biochem. Pharmacol., 62: 1587–1595, 2001. [DOI] [PubMed] [Google Scholar]
78. Badawi A.F., Badr M.Z., Chemoprevention of breast cancer by targeting cyclooxygenase‐2 and peroxisome proliferator‐activated receptor‐gamma (Review), Int. J. Oncol. 20: 1109–1122, 2002. [PubMed] [Google Scholar]
79. Holford N.H.G., Benet L.Z., Pharmacokinetics and Pharmacodynamics: rational dose selection and the time course of drug action In: Katzung B.G., ed., Basic and Clincal Pharmacology. 6th edition, Appleton & Lange, Norwalk , Connecticut , 1995, pp 33–48. [Google Scholar]
80. Koki A.T., Leahy K.M., Masferrer J.L., Potential utility of COX‐2 inhibitors in chemoprevention and chemotherapy. Expert Opin. Investig. Drugs 8: 1623–1638, 1999. [DOI] [PubMed] [Google Scholar]
81. Sano H., Kawahito Y., Wilder R.L., Hashiramoto A., Mukai S., Asai K., Kimura S., Kato H., Kondo M., Hla T., Expression of cyclooxygenase‐1 and −2 in human colorectal cancer, Cancer Res., 55: 3785–3789, 1995. [PubMed] [Google Scholar]
82. Molina M.A., Sitja‐Arnau M., Lemoine M.G., Frazier M.L., Sinicrope F.A., Increased cyclooxygenase‐2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti‐inflammatory drugs, Cancer Res., 59: 4356–4362, 1999. [PubMed] [Google Scholar]
83. Ristimaki A., Honkanen N., Jankala H., Sipponen P., Harkonen M., Expression of cyclooxygenase‐2 in human gastric carcinoma, Cancer Res., 57: 1276–1280, 1997. [PubMed] [Google Scholar]
84. Uefuji K., Ichikura T., Mochizuki H., Shinomiya N., Expression of cyclooxygenase‐2 protein in gastric adenocarcinoma, J. Surg. Oncol., 69: 168–172, 1998. [DOI] [PubMed] [Google Scholar]
85. Tsujii M., DuBois R.N., Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2, Cell, 83: 493–50, 1995. [DOI] [PubMed] [Google Scholar]
86. Oshima M., Dinchuk J.E., Kargman S.L., Oshima H., Hancock B., Kwong E., Trzaskos J.M., Evans J.F., Taketo M.M., Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX‐2), Cell, 87: 803–809, 1996. [DOI] [PubMed] [Google Scholar]
87. Liu C.H., Chang S.H., Narko K., Trifan O.C., Wu M.T., Smith E., Haudenschild C., Lane T.F., Hla T., Overexpression of cyclooxygenase‐2 is sufficient to induce tumorigenesis in transgenic mice, J. Biol. Chem., 276: 18563–18569, 2001. [DOI] [PubMed] [Google Scholar]
88. Kinoshita T., Takahashi Y., Sakashita T., Inoue H., Tanabe T., Yoshimoto T., Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells, Biochim. Biophys. Acta, 1438: 120–130, 1999. [DOI] [PubMed] [Google Scholar]
89. Hashimoto N., Watanabe T., Ikeda Y., Yamada H., Taniguchi S., Mitsui H., Kurokawa K., Prostaglandins induce proliferation of rat hepatocytes through a prostaglandin E2 receptor EP3 subtype, Am. J. Physiol., 272: G597–G604, 1997. [DOI] [PubMed] [Google Scholar]
90. Kimura M., Osumi S., Ogihara M., Prostaglandin E(2) (EP(1)) receptor agonist‐induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes: the involvement of TGF‐alpha, Endocrinology, 142: 4428–4440, 2001. [DOI] [PubMed] [Google Scholar]
91. Pentland A.P., Needleman P., Modulation of keratinocyte proliferation in vitro by endogenous prostaglandin synthesis, J. Clin. Invest., 77: 246–251, 1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
92. Bandyopadhyay G.K., Imagawa W., Wallace D., Nandi S., Linoleate metabolites enhance the in vitro proliferative response of mouse mammary epithelial cells to epidermal growth factor, J. Biol. Chem., 262: 2750–2756, 1987. [PubMed] [Google Scholar]
93. Nolan R.D., Danilowicz R.M., Eling T.E., Role of arachidonic acid metabolism in the mitogenic response of BALB/c 3T3 fibroblasts to epidermal growth factor, Mol. Pharmacol., 33: 650–656, 1988. [PubMed] [Google Scholar]
94. Quarles L.D., Haupt D.M., Davidai G., Middleton J.P., Prostaglandin F2 alpha‐induced mitogenesis in MC3T3‐E1 osteoblasts: role of protein kinase‐C‐mediated tyrosine phosphorylation, Endocrinology, 132: 1505–1513, 1993. [DOI] [PubMed] [Google Scholar]
95. Goin M., Pignataro O., Jimenez de Asua L., Early cell cycle diacylglycerol (DAG) content and protein kinase C (PKC) activity enhancement potentiates prostaglandin F2 alpha (PGF2 alpha) induced mitogenesis in Swiss 3T3 cells, FEBS Lett., 316: 68–72, 1993. [DOI] [PubMed] [Google Scholar]
96. Zhao Y., Agarwal V.R., Mendelson C.R., Simpson E.R., Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene, Endocrinology, 137: 5739–5742, 1996. [DOI] [PubMed] [Google Scholar]
97. Harris R.E., Robertson F.M., Abou‐Issa H.M., Farrar W.B., Brueggemeier R., Genetic induction and upregulation of cyclooxygenase (COX) and aromatase (CYP19): an extension of the dietary fat hypothesis of breast cancer, Med. Hypotheses, 52: 291–292, 1999. [DOI] [PubMed] [Google Scholar]
98. McKanna J.A., Zhang M.Z., Wang J.L., Cheng H., Harris R.C., Constitutive expression of cyclooxygenase 2 in rat vas deferens, Am. J. Physiol., 275: R227–R233, 1998. [DOI] [PubMed] [Google Scholar]
99. Lyson K., Indomethacin suppression of the estradiol induced proliferative response of the seminal vesicles, Exp. Clin. Endocrinol., 84: 223–227, 1984. [PubMed] [Google Scholar]
100. Fürstenberger G., Marks F., Indomethacin inhibition of cell proliferation induced by the phorbolester TPA is reversed by prostaglandin E2 in mouse epidermis in vivo, Biochem. Biophys. Res. Commun., 84: 1103–1111, 1978. [DOI] [PubMed] [Google Scholar]
101. Verma A.K., Ashendel C.L., Boutwell R.K., Inhibition by prostaglandin synthesis inhibitors of the induction of epidermal ornithine decarboxylase activity, the accumulation of prostaglandins and tumor promotion caused by 12 O tetradecanoylphorbol 13 acetate, Cancer Res., 40: 308–315, 1980. [PubMed] [Google Scholar]
102. Marnett L.J., Aspirin and the potential role of prostaglandins in colon cancer, Cancer Res., 52: 5575–5589, 1992. [PubMed] [Google Scholar]
103. Sun Y., Tang X.M., Half E., Kuo M.T., Sinicrope F.A., Cyclooxygenase‐2 overexpression reduces apoptotic susceptibility by inhibiting the cytochrome c‐dependent apoptotic pathway in human colon cancer cells, Cancer Res., 62: 6323–6328, 2002. [PubMed] [Google Scholar]
104. Ottonello L., Gonella R., Dapino P., Sacchetti C., Dallegri F., Prostaglandin E2 inhibits apoptosis in human neutrophilic polymorphonuclear leukocytes: role of intracellular cyclic AMP levels, Exp. Hematol., 26: 895–902, 1998. [PubMed] [Google Scholar]
105. Kawamura T., Horie S., Maruyama T., Akira T., Imagawa T., Nakamura N., Prostaglandin E1 transported into cells blocks the apoptotic signals induced by nerve growth factor deprivation, J. Neurochem., 72: 1907–1914, 1999. [DOI] [PubMed] [Google Scholar]
106. Kroll B., Kunz S., Tu N., Schwarz L.R., Inhibition of transforming growth factor‐beta1 and UV light‐induced apoptosis by prostanoids in primary cultures of rat hepatocytes, Toxicol. Appl. Pharmacol., 152: 240–250, 1998. [DOI] [PubMed] [Google Scholar]
107. Kliewer S.A., Lenhard J.M., Willson T.M., Patel I., Morris D.C., Lehmann J.M., A prostaglandin J2 metabolite binds peroxisome proliferator‐activated receptor gamma and promotes adipocyte differentiation, Cell, 83: 813–819, 1995. [DOI] [PubMed] [Google Scholar]
108. Fitzpatrick F.A., Wynalda M.A., Albumin‐catalyzed metabolism of prostaglandin D2, J. Biol. Chem., 258: 11713–11718, 1983. [PubMed] [Google Scholar]
109. Demetri G.D., Fletcher C.D., Mueller E., Sarraf P., Naujoks R., Campbell N., Spiegelman B.M., Singer S., Induction of solid tumor differentiation by the peroxisome proliferator‐activated receptor‐gamma ligand troglitazone in patients with liposarcoma, Proc. Natl. Acad. Sci. U.S.A., 96: 3951–3956, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
110. Clay C.E., Namen A.M., Fonteh A.N., Atsumi G., High K.P., Chilton F.H., 15‐deoxy‐Delta(12,14)PGJ(2) induces diverse biological responses via PPARgamma activation in cancer cells, Prostaglandins Other Lipid. Mediat., 62: 23–32, 2000. [DOI] [PubMed] [Google Scholar]
111. Ricote M., Li A.C., Willson T.M., Kelly C.J., Glass C.K., The peroxisome proliferator‐activated receptorgamma is a negative regulator of macrophage activation, Nature, 391: 79–82, 1998. [DOI] [PubMed] [Google Scholar]
112. Bishop‐Bailey D., and Hla T., Endothelial cell apoptosis induced by the peroxisome proliferator‐activated receptor (PPAR) ligand 15‐deoxy‐Delta12, 14‐prostaglandin J2, J. Biol. Chem., 274, 17042–17048, 1999. [DOI] [PubMed] [Google Scholar]
113. Xin X., Yang S., Kowalski J., Gerritsen M.E., Peroxisome proliferator‐activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo, J. Biol. Chem., 274: 9116–9121, 1999. [DOI] [PubMed] [Google Scholar]
114. Takashima T., Fujiwara Y., Higuchi K., Arakawa T., Yano Y., Hasuma T., Otani S., PPARgamma ligands inhibit growth of human esophageal adenocarcinoma cells through induction of apoptosis, cell cycle arrest and reduction of ornithine decarboxylase activity, Int. J. Oncol., 19: 465–471, 2001. [PubMed] [Google Scholar]
115. Shimada T., Kojima K., Yoshiura K., Hiraishi H., Terano A., Characteristics of the peroxisome proliferator activated receptor gamma (PPARgamma) ligand induced apoptosis in colon cancer cells, Gut, 50: 658–64, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
116. Girnun G.D., Smith W.M., Drori S., Sarraf P., Mueller E., Eng C., Nambiar P., Rosenberg D.W., Bronson R.T., Edelmann W., Kucherlapati R., Gonzalez F.J., Spiegelman B.M., APC‐dependent suppression of colon carcinogenesis by PPAR gamma, Proc. Natl. Acad. Sci. U.S.A., 99: 13771–13776, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
117. Yamakawa K., Hosoi M., Koyama H., Tanaka S., Fukumoto S., Morii H., Nishizawa Y., Peroxisome proliferator‐activated receptor‐gamma agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells, Biochem. Biophys. Res. Commun., 271: 571–574, 2000. [DOI] [PubMed] [Google Scholar]
118. Haslmayer P., Thalhammer T., Jager W., Aust S., Steiner G., Ensinger C., Obrist P., The peroxisome proliferator‐activated receptor gamma ligand 15‐deoxy‐Delta12,14‐prostaglandin J2 induces vascular endothelial growth factor in the hormone‐independent prostate cancer cell line PC 3 and the urinary bladder carcinoma cell line 5637, Int. J. Oncol., 21: 915–920, 2002. [PubMed] [Google Scholar]
119. Bunting S., Gryglewski R., Moncada S., Vane J.R., Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which re‐laxes strips of mesenteric and coeliac ateries and inhibits platelet aggregation, Prostaglandins, 12: 897–913, 1976. [DOI] [PubMed] [Google Scholar]
120. Whittle B.J., Moncada S., Whiting F., Vane J.R., Carbacyclin‐a potent stable prostacyclin analogue for the inhibition of platelet aggregation, Prostaglandins, 19: 605–627, 1980. [DOI] [PubMed] [Google Scholar]
121. Baxter G.S., Clayton J.K., Coleman R.A., Marshall K., Sangha R., Senior J., Characterization of the prostanoid receptors mediating constriction and re‐laxation of human isolated uterine artery, Br. J. Pharmacol., 116: 1692–1696, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
122. Lim H., Dey S.K., A novel pathway of prostacyclin signaling‐hanging out with nuclear receptors, Endocrinology, 143: 3207–3210, 2002. [DOI] [PubMed] [Google Scholar]
123. Gupta R.A., Tan J., Krause W.F., Geraci M.W., Willson T.M., Dey S.K., DuBois R.N., Prostacyclin‐mediated activation of peroxisome proliferator‐activated receptor‐δ in colorectal cancer, Proc. Natl. Acad. Sci. U.S.A., 97: 13275–13280, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
124. Roy, H. K. , Karolski, W. J. , Ratashak, A. , Distal bowel selectivity in the chemoprevention of experimental colon carcinogenesis by the non‐steroidal anti‐inflammatory drug nabumetone, Int. J. Cancer, 92: 609–615, 2001. [DOI] [PubMed] [Google Scholar]
125. Tong B.J., Tan J., Tajeda L., Das S.K., Chapman J.A., DuBois R.N., Dey S.K., Heightened expression of cyclooxygenase‐2 and peroxisome proliferator‐activated receptor‐δ in human endometrial adenocarcinoma, Neoplasia, 2: 483–490, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
126. Park, B. H. , Vogelstein, B. , Kinzler, K. W. , Genetic disruption of PPARδ decreases the tumorigenicity of human colon cancer cells, Proc. Natl. Acad. Sci. U.S.A., 98: 2598–2603, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
127. Barak, Y. , Liao, D. , He, W. , Ong, E. S. , Nelson, M. C. , Olefsky, J. M. , Boland, R. , Evans, R. M. , Effects of peroxisome proliferator‐activated receptor‐δ on placentation, adiposity, and colorectal cancer, Proc. Natl. Acad. Sci. U.S.A., 99: 303–308, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
128. Shao J., Sheng H., DuBois R.N., Peroxisome proliferatoractivated receptors modulate K‐Ras‐mediated transformation of intestinal epithelial cells, Cancer Res., 62: 3282–3288, 2002. [PubMed] [Google Scholar]
129. Takahashi K., Sawasaki Y., Hata J., Mukai K., Goto T., Spontaneous transformation and immortalization of human endothelial cells, In Vitro Cell & Dev. Biol., 26: 265–274, 1990. [DOI] [PubMed] [Google Scholar]
130. Brown J., Reading S.J., Jones S., Fitchett C.J., Howl J., Martin A., Longland C.L., Michelangeli F., Dubrova Y.E., Brown C.A., Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83, Lab. Invest., 80w: 37–45, 2000. [DOI] [PubMed] [Google Scholar]
131. Narko K., Ristimaki A., MacPhee M., Smith E., Haudenschild C.C., Hla T., Tumorigenic transformation of immortalized ECV endothelial cells by cyclooxygenase‐1 overexpression, J. Biol. Chem., 272: 21455–21460, 1997. [DOI] [PubMed] [Google Scholar]
132. No D., Yao T.P., Evans R.M., Ecdysone‐inducible gene expression in mammalian cells and transgenic mice, Proc. Natl. Acad. Sci. U.S.A., 93: 3346–3351, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
133. Trifan O.C., Smith R.M., Thompson B.D., Hla T., Overexpression of cyclooxygenase‐2 induces cell‐cycle arrest: evidence for a prostaglandin‐independent mechanism, J Biol. Chem., 274: 34141–34147, 1999. [DOI] [PubMed] [Google Scholar]
134. Lecomte, M. , Laneuville, O. , Ji, C. , DeWitt, D.L. , Smith, W.L. , Acetylation of human prostaglandin endoperoxide synthase‐2 (cyclooxygenase‐2) by aspirin, J. Biol. Chem., 269: 13207–13215, 1994. [PubMed] [Google Scholar]
135. Zahner G., Wolf G., Ayoub M., Reinking R., Panzer U., Shankland S.J., Stahl R.A., Cyclooxygenase‐2 overexpression inhibits platelet‐derived growth factor‐induced mesangial cell proliferation through induction of the tumor suppressor gene p53 and the cyclin‐dependent kinase inhibitors p21waf‐1/cip‐1 and p27kip‐1, J. Biol. Chem., 277: 9763–9771, 2002. [DOI] [PubMed] [Google Scholar]
136. DuBois R.N., Abramson S.B., Crofford L., Gupta R.A., Simon L.S., Van De Putte L.B., and Lipsky P.E., Cyclooxygenase in biology and disease, FASEB J 12: 1063–1073, 1998. [PubMed] [Google Scholar]
137. Munroe, D.G. , Wang, E.Y. , MacIntyre, J.P. , Tam, S.S. , Lee, D.H. , Taylor, G.R. , Zhou, L. , Plante, R.K. , Kazmi, S.M. , Bauerle, P.A. , et al. Novel intracellular signaling function of prostaglandin H synthase‐1 in NF‐kappa B activation, J. Inflamm., 45: 260–268, 1995. [PubMed] [Google Scholar]
138. Ballif B.A., Mincek N.V., Barratt J.T., Wilson M.L., Simmons D.L., Interaction of cyclooxygenases with an apoptosis‐ and autoimmunity‐associated protein, Proc. Natl. Acad. Sci. U.S.A., 93: 5544–5549, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
139. Leahy, K.M. , Ornberg, R.L. , Wang, Y. , Zweifel, B.S. , Koki, A.T. , Masferrer J.L., Cyclooxygenase‐2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo , Cancer Res., 62: 625–31, 2002. [PubMed] [Google Scholar]
140. Karim, A. , Boynton, J. , Wallemark, C. , Kent, J. , Frazier‐O'Bannon, L. , Effects of celecoxib (cyp2c9 substrate) and omeprazole (cyp2c9 substrate /inhibitor) on systemic exposure to each other, AAPS. Pharm. Sci., 3: T3669 (Abstr.), 2001. [Google Scholar]

[b1] 1. Smith W.L., The eicosanoids and their biochemical mechanisms of action, Biochem. J., 259: 315–324, 1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b2] 2. Hla T. Ristimaki A., Appleby S., Barriocanal J. G., Cyclooxygenase gene expression in inflammation and angiogenesis, Ann. N. Y. Acad. Sci., 696: 197–204, 1993. [DOI] [PubMed] [Google Scholar]

[b3] 3. Schror K., The effect of prostaglandins and thromboxane A2 on coronary vessel tone‐mechanisms of action and therapeutic implications, Eur. Heart. J., 14(Suppl I): 34–41, 1993. [PubMed] [Google Scholar]

[b4] 4. Davies P., Bailey P.J., Goldenberg M.M., Ford‐Hutchinson A.W., The role of arachidonic acid oxygenation products in pain and inflammation, Annu. Rev. Immunol., 2: 335–357, 1984. [DOI] [PubMed] [Google Scholar]

[b5] 5. Vane J.R., Botting R.M., Anti‐inflammatory drugs and their mechanism of action, Inflamm. Res., 47(Suppl 2): S78–S87, 1998. [DOI] [PubMed] [Google Scholar]

[b6] 6. Futaki N., Takahashi S., Yokoyama M., Arai I., Higuchi S., Otomo S., NS‐398, a new anti‐inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX‐2) activity in vitro , Prostaglandins, 47: 55–59, 1994. [DOI] [PubMed] [Google Scholar]

[b7] 7. Smith C.J., Zhang Y., Koboldt C.M., Muhammad J., Zweifel B.S., Shaffer A., Talley J.J., Masferrer J.L., Seibert K., Isakson P.C., Pharmacological analysis of cyclooxygenase‐1 in inflammation, Proc. Natl. Acad. Sci. U.S.A., 95: 13313–13318, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b8] 8. Chan C.C., Boyce S., Brideau C., Charleson S., Cromlish W., Ethier D., Evans J., Ford‐Hutchinson A.W., Forrest M.J., Gauthier J.Y., et al., Rofecoxib [Vioxx, MK‐0966; 4‐(4′‐methylsulfonylphenyl)‐3‐phenyl‐2‐(5H)‐furanone]: a potent and orally active cyclooxygenase‐2 inhibitor. Pharmacological and biochemical profiles, J. Pharmacol. Exp. Ther., 290: 551–560, 1999. [PubMed] [Google Scholar]

[b9] 9. McAdam B.F., Catella‐Lawson F., Mardini I.A., Kapoor S., Lawson J.A., FitzGerald G.A., Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)‐2: the human pharmacology of a selective inhibitor of COX‐2, Proc. Natl. Acad. Sci. U.S.A., 96: 272–277, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b10] 10. Smith W.L., DeWitt D.L., Prostaglandin endoperoxide H synthases‐1 and −2, Adv. Immunol., 62: 167–215, 1996. [DOI] [PubMed] [Google Scholar]

[b11] 11. Sirois J., Simmons D.L., Richards J.S., Hormonal regulation of messenger ribonucleic acid encoding a novel isoform of prostaglandin endoperoxide H synthase in rat preovulatory follicles. Induction in vivo and in vitro, J. Biol. Chem., 267: 11586–11592, 1992. [PubMed] [Google Scholar]

[b12] 12. O'Sullivan M.G., Chilton F.H., Huggins E.M. Jr, McCall C.E., Lipopolysaccharide priming of alveolar macrophages for enhanced synthesis of prostanoids involves induction of a novel prostaglandin H synthase, J. Biol. Chem., 267: 14547–14550, 1992. [PubMed] [Google Scholar]

[b13] 13. Evett G.E., Xie W., Chipman J.G., Robertson D.L., Simmons D.L., Prostaglandin G/H synthase isoenzyme 2 expression in fibroblasts: regulation by dexamethasone, mitogens, and oncogenes, Arch. Biochem. Biophys., 306: 169–177, 1993. [DOI] [PubMed] [Google Scholar]

[b14] 14. DeWitt D.L., Meade E.A., Serum and glucocorticoid regulation of gene transcription and expression of the prostaglandin H synthase‐1 and prostaglandin H synthase‐2 isozymes, Arch. Biochem. Biophys., 306: 94–102, 1993. [DOI] [PubMed] [Google Scholar]

[b15] 15. Jones D.A., Carlton D.P., McIntyre T.M., Zimmerman G.A., Prescott S.M., Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines, J. Biol. Chem., 268: 9049–9054, 1993. [PubMed] [Google Scholar]

[b16] 16. Smith W. L., Garavito R. M., DeWitt D. L., Prostaglandin endoperoxide H synthase (Cyclooxygenases)‐1 and −2, J. Biol. Chem., 271: 33157–33160, 1996. [DOI] [PubMed] [Google Scholar]

[b17] 17. Simon L.S., Role and regulation of cyclooxygenase‐2 during inflammation, Am. J. Med., 106: 37S–42S, 1999. [DOI] [PubMed] [Google Scholar]

[b18] 18. Hla T., Neilson K., Human cyclooxygenase‐2 cDNA, Proc. Natl. Acad. Sci. USA, 89: 7384–7388, 1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b19] 19. Kraemer S. A., Meade E. A., DeWitt D. L., Prostaglandin endoperoxide synthase gene structure: identification of the transcriptional start site and 5′‐flanking regulatory sequences, Arch. Biochem. Biophys., 293: 391–400, 1992. [DOI] [PubMed] [Google Scholar]

[b20] 20. Kujubu D. A., Herschman H. R., Dexamethasone inhibits mitogen induction of the TIS10 prostaglandin synthase/cyclooxygenase gene, J. Biol. Chem., 267: 7991–7994, 1992. [PubMed] [Google Scholar]

[b21] 21. Reddy S.T., Herschman H. R., Prostaglandin synthase‐1 and prostaglandin synthase‐2 are coupled to distinct phospholipases for the generation of prostaglandin D2 in activated mast cells, J. Biol. Chem., 272: 3231–3237, 1997. [DOI] [PubMed] [Google Scholar]

[b22] 22. Devchand P. R., Keller H., Peters J. M., Vazquez M., Gonzalez F. J., Wahli W., The PPARalpha‐leukotriene B4 pathway to inflammation control, Nature, 384: 39–43, 1996. [DOI] [PubMed] [Google Scholar]

[b23] 23. Forman B. M., Tontonoz P., Chen J., Brun R. P., Spiegelman B. M., Evans R. M., 15‐Deoxy‐delta 12, 14‐prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma, Cell, 83: 803–812, 1995. [DOI] [PubMed] [Google Scholar]

[b24] 24. Morita I., Schindler M., Regier M.K., Otto J.C., Hori T., DeWitt D.L., Smith W.L., Different intracellular locations for prostaglandin endoperoxide H synthase‐1 and −2, J. Biol. Chem., 270: 10902–10908, 1995. [DOI] [PubMed] [Google Scholar]

[b25] 25. Spencer A. G., Woods J. W., Arakawa T., Singer I. I., Smith W. L., Subbcellular localization of Prostaglandin endoperoxide H synthase‐1 and −2 by immunoelectron microscopy, J.Biol. Chem., 273: 9886–9893, 1998. [DOI] [PubMed] [Google Scholar]

[b26] 26. Tontonoz P., Hu E., Spiegelman B. M., Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid activated transcription factor, Cell, 79: 1147–1156, 1994. [DOI] [PubMed] [Google Scholar]

[b27] 27. Howe L.R., Subbaramaiah K., Chung W.J., Dannenberg A.J., Brown A.M., Transcriptional activation of cyclooxygenase‐2 in Wnt‐1‐transformed mouse mammary epithelial cells, Cancer Res., 59: 1572–1577, 1999. [PubMed] [Google Scholar]

[b28] 28. Roman C.D., Morrow J., Whitehead R., Beauchamp R.D., Induction of cyclooxygenase‐2 and invasiveness by transforming growth factor‐beta(1) in immortalized mouse colonocytes expressing oncogenic Ras, J. Gastrointest. Surg., 6: 304–309, 2002. [DOI] [PubMed] [Google Scholar]

[b29] 29. Sheng, H. , Williams, C. S. , Shao, J. , Liang, P. , DuBois, R. N. , Beauchamp, R. D. , Induction of cyclooxygenase‐2 by activated Ha‐ras oncogene in Rat‐1 fibroblasts and the role of mitogen‐activated protein kinase pathway, J. Biol. Chem., 273: 22120–22127, 1998. [DOI] [PubMed] [Google Scholar]

[b30] 30. Sheng, G. G. , Shao, J. , Sheng, H. , Hooton, E. B. , Isakson, P. C. , Morrow, J. D. , Coffey, R. J. , DuBois, R. N. , Beauchamp, R. D. , A selective cyclooxygenase 2 inhibitor suppresses the growth of H‐ras‐transformed rat intestinal epithelial cells, Gastroenterology, 113: 1883–1891, 1997. [DOI] [PubMed] [Google Scholar]

[b31] 31. Subbaramaiah, K. , Telang, N. , Ramonetti, J. T. , Araki, R. , DeVito, B. , Weksler, B. B. , Dannenberg, A. J. , Transcription of cyclooxygenase‐2 is enhanced in transformed mammary epithelial cells, Cancer Res., 56: 4424–4429, 1996. [PubMed] [Google Scholar]

[b32] 32. Heasley, L. E. , Thaler, S. , Nicks, M. , Price, B. , Skorecki, K. , Nemenoff, R. A. , Induction of cytosolic phospholipase A2 by oncogenic Ras in human non‐small cell lung cancer, J. Biol. Chem., 272, 14501–14504, 1997. [DOI] [PubMed] [Google Scholar]

[b33] 33. Ristimaki A., Garfinkel S., Wessendorf J., Maciag T., Hla T., Induction of cyclooxygenase‐2 by interleukin‐1 alpha. Evidence for post‐transcriptional regulation, J. Biol. Chem., 269: 11769–11775, 1994. [PubMed] [Google Scholar]

[b34] 34. Yamamoto K., Arakawa T., Ueda N., Yamamoto S., Transcriptional roles of nuclear factor kappa B and nuclear factor‐interleukin‐6 in the tumor necrosis factor alphadependent induction of cyclooxygenase‐2 in MC3T3‐E1 cells, J. Biol. Chem., 270: 31315–31320, 1995. [DOI] [PubMed] [Google Scholar]

[b35] 35. Liu S.F., Ye X., Malik A.B., Inhibition of NF‐kappaB activation by pyrrolidine dithiocarbamate prevents in vivo expression of proinflammatory genes, Circulation, 100: 1330–1337, 1999. [DOI] [PubMed] [Google Scholar]

[b36] 36. Matsuura H., Sakaue M., Subbaramaiah K., Kamitani H., Eling T.E., Dannenberg A.J., Tanabe T., Inoue H., Arata J., Jetten A.M., Regulation of cyclooxygenase‐2 by interferon gamma and transforming growth factor alpha in normal human epidermal keratinocytes and squamous carcinoma cells, J. Biol. Chem., 274: 29138–29148, 1999. [DOI] [PubMed] [Google Scholar]

[b37] 37. Nakagawa T., Fujita N., Oh‐Hara T., Kurokawa T., Nakamura K., Tsuruo T., Interleukin‐1 alpha induced cyclooxygenase‐2 expression in bone‐derived endothelial cells, J. Cell. Physiol., 179: 226–232, 1999. [DOI] [PubMed] [Google Scholar]

[b38] 38. Kage K., Fujita N., Oh‐hara T., Ogata E., Fujita T., Tsuruo T., Basic fibroblast growth factor induces cyclooxygenase‐2 expression in endothelial cells derived from bone, Biochem. Biophys. Res. Commun., 254: 259–263, 1999. [DOI] [PubMed] [Google Scholar]

[b39] 39. Kirtikara K., Laulederkind S. J., Raghow R., Kanekura T., Ballou L. R., An accessory role for ceramide in interleukin‐1beta induced prostaglandin synthesis, Mol. Cell. Biochem., 181: 41–48, 1998. [DOI] [PubMed] [Google Scholar]

[b40] 40. Blanco A., Habib A., Levy‐Toledano S., Maclouf J., Involvement of tyrosine kinases in the induction of cyclooxygenase‐2 in human endothelial cells, Biochem. J., 312: 419–423, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b41] 41. Kennelly P.J., Krebs E.G., Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases, J. Biol. Chem., 266: 15555–15558, 1991. [PubMed] [Google Scholar]

[b42] 42. Vezza R., Habib A., Li H., Lawson J. A., FitzGerald G.A., Regulation of cyclooxygenases by protein kinase C. Evidence against the importance of direct enzyme phosphorylation, J. Biol. Chem., 271: 30028–30033, 1996. [DOI] [PubMed] [Google Scholar]

[b43] 43. Schmedtje J. F. Jr., Ji Y‐S., Liu W. ‐L., DuBois R. N., Runge S. M., Hypoxia induces cyclooxygenase‐2 via the NF‐kB p65 transcription factor in human vascular endothelial cells, J. Biol. Chem., 272: 601–608, 1997. [DOI] [PubMed] [Google Scholar]

[b44] 44. Shweiki D., Itin A., Soffer D., Keshet E., Vascular endothelial growth factor induced by hypoxia may mediate hypoxia‐initiated angiogenesis, Nature 359: 843–845, 1992. [DOI] [PubMed] [Google Scholar]

[b45] 45. Levy G. N., Prostaglandin H synthases, nonsteroidal antiinflammatory drugs, and colon cancer, FASEB J., 11: 234–247, 1997. [PubMed] [Google Scholar]

[b46] 46. Rosenberg L., Louik C., Shapiro S., Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma, Cancer 82: 2326–2333, 1998. [DOI] [PubMed] [Google Scholar]

[b47] 47. Giardiello. F.M. , Offerhaus. G.J. , DuBois. R.N. , The role of nonsteroidal anti‐inflammatory drugs in colorectal cancer prevention, Eur. J. Cancer, 31A: 1071–1076, 1995. [DOI] [PubMed] [Google Scholar]

[b48] 48. Reddy B.S., Maruyama H., Kelloff G., Dose‐related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal antiinflammatory drug, during different stages of rat colon tumor development, Cancer Res., 47: 5340–5346, 1987. [PubMed] [Google Scholar]

[b49] 49. Masferrer J.L., Leahy K.M., Koki A.T., Zweifel B.S., Settle S.L., Woerner B.M., Edwards D.A., Flickinger A.G., Moore R.J., Seibert K., Antiangiogenic and antitumor activities of cyclooxygenase‐2 inhibitors, Cancer Res., 60: 1306–11, 2000. [PubMed] [Google Scholar]

[b50] 50. Trifan O.C., Durham W.F., Salazar V., Horton J., Levine B.D., Zweifel B.S., Davis T.W., Masferrer J.L., COX‐2 inhibition with celecoxib enhances anti‐tumor efficacy and reduces diarrhea side effect of CPT‐11, Cancer Res., 62: 5778–5784, 2002. [PubMed] [Google Scholar]

[b51] 51. Zweifel B.S., Davis T.W., Ornberg R.L., Masferrer J.L., Direct evidence for a role of cyclooxygenase 2‐derived prostaglandin E2 in human head and neck xenograft tumors, Cancer Res., 62: 6706–6711, 2002. [PubMed] [Google Scholar]

[b52] 52. Peterson H.I., Effects of prostaglandin synthesis inhibitors on tumor growth and vascularization. Experimental studies in the rat, Invasion Metastasis, 3: 151–159, 1983. [PubMed] [Google Scholar]

[b53] 53. Tsujii M., Kawano S., Tsuji S., Sawaoka H., Hori M., DuBois R.N., Cyclooxygenase regulates angiogenesis induced by colon cancer cells, Cell 93: 705–716, 1998. [DOI] [PubMed] [Google Scholar]

[b54] 54. Chu J., Lloyd F.L., Trifan O.C., Knapp B., Rizzo M.T., Potential involvement of the cyclooxygenase‐2 pathway in the regulation of tumor‐associated angiogenesis and growth in pancreatic cancer, Mol. Cancer Ther., 2: 1–7, 2003. [PubMed] [Google Scholar]

[b55] 55. Majima M., Isono M., Ikeda Y., Hayashi I., Hatanaka K., Harada Y., Katsumata O., Yamashina S., Katori M., Yamamoto S., Significant roles of inducible cyclooxygenase (COX)‐2 in angiogenesis in rat sponge implants, Jpn. J. Pharmacol., 75: 105–114, 1997. [DOI] [PubMed] [Google Scholar]

[b56] 56. Daniel T.O., Liu H., Morrow J.D., Crews B.C., Marnett L.J., Thromboxane A2 is a mediator of cyclooxygenase‐2‐dependent endothelial migration and angiogenesis, Cancer Res., 59: 4574–4577, 1999. [PubMed] [Google Scholar]

[b57] 57. Sawaoka H., Tsuji S., Tsujii M., Gunawan E.S., Sasaki Y., Kawano S., Hori M., Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo, Lab. Invest., 79: 1469–77, 1999. [PubMed] [Google Scholar]

[b58] 58. Masferrer J.L., Koki A., Seibert K., COX‐2 inhibitors. A new class of antiangiogenic agents, Ann. N. Y. Acad. Sci., 889: 84–68, 1999. [DOI] [PubMed] [Google Scholar]

[b59] 59. Yamada M., Kawai M., Kawai Y., Mashima Y., The effect of selective cyclooxygenase‐2 inhibitor on corneal angiogenesis in the rat, Curr. Eye Res., 19: 300–304, 1999. [DOI] [PubMed] [Google Scholar]

[b60] 60. Qiao L., Shiff S.J., Rigas B., Sulindac sulfide inhibits the proliferation of colon cancer cells: diminished expression of the proliferation markers PCNA and Ki‐67, Cancer Lett., 115, 229–234, 1997. [DOI] [PubMed] [Google Scholar]

[b61] 61. Zhang X., Morham S.G., Langenbach R., Young D.A., Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase‐null embryo fibroblasts, J. Exp. Med., 190, 451–459, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b62] 62. Hara A., Yoshimi N., Niwa M., Ino N., Mori H., Apoptosis induced by NS‐398, a selective cyclooxygenase‐2 inhibitor, in human colorectal cancer cell lines, Jpn. J. Cancer Res., 88: 600–604, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b63] 63. Ding X.Z., Tong W.G., Adrian T.E., Blockade of cyclooxygenase‐2 inhibits proliferation and induces apoptosis in human pancreatic cancer cells, Anticancer Res., 20: 2625–31, 2000. [PubMed] [Google Scholar]

[b64] 64. Hida T., Kozaki K., Muramatsu H., Masuda A., Shimizu S., Mitsudomi T., Sugiura T., Ogawa M., Takahashi T., Cyclooxygenase‐2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non‐small cell lung cancer cell lines, Clin. Cancer Res., 6: 2006–2011, 2000. [PubMed] [Google Scholar]

[b65] 65. Hanif R., Pittas A., Feng Y., Koutsos M.I., Qiao L., Staiano‐Coico L., Shiff S.I., Rigas B., Effects of nonsteroidal anti‐inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin‐independent pathway, Biochem. Pharmacol., 52: 237–245, 1996. [DOI] [PubMed] [Google Scholar]

[b66] 66. Elder D.J., Hague A., Hicks D.J., Paraskeva C., Different growth inhibition by the aspirin metabolite salicylate in human colorectal tumor cell lines: enhanced apoptosis in carcinoma and in vitro transformed adenoma relative to adenoma cell lines, Cancer Res., 56: 2273–2276, 1996. [PubMed] [Google Scholar]

[b67] 67. Grosch S., Tegeder I., Niederberger E., Brautigam L., Geisslinger G., COX‐2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX‐2 inhibitor celecoxib, FASEB J., 15: 2742–2744, 2001. [DOI] [PubMed] [Google Scholar]

[b68] 68. Richter M., Weiss M., Weinberger I., Furstenberger G., Marian B., Growth inhibition and induction of apoptosis in colorectal tumor cells by cyclooxygenase inhibitors, Carcinogenesis, 22: 17–25, 2001. [DOI] [PubMed] [Google Scholar]

[b69] 69. Rigas B., Shiff S.J., Is inhibition of cyclooxygenase required for the chemopreventive effect of NSAIDs in colon cancer A model reconciling the current contradiction, Med. Hypotheses, 54: 210–5, 2000. [DOI] [PubMed] [Google Scholar]

[b70] 70. Hsu A.L., Ching T.T., Wang D.S., Song X., Rangnekar V.M., Chen C.S., The cyclooxygenase‐2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl‐2, J. Biol. Chem., 275: 11397–11403, 2000. [DOI] [PubMed] [Google Scholar]

[b71] 71. Grilli M., Pizzi M., Memo M., Spano P., Neuroprotection by aspirin and sodium salicylate through blockade of NF‐kappaB activation, Science, 274: 1383–1385, 1996. [DOI] [PubMed] [Google Scholar]

[b72] 72. Yin M.J., Yamamoto Y., Gaynor R.B., The anti‐inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase‐beta, Nature, 396: 77–78, 1998. [DOI] [PubMed] [Google Scholar]

[b73] 73. Yamamoto Y., Yin M.J., Lin K.M., Gaynor R.B., Sulindac inhibits activation of the NF‐kappaB pathway, J. Biol. Chem., 274: 27307–27314, 1999. [DOI] [PubMed] [Google Scholar]

[b74] 74. Stark L.A., Din F.V., Zwacka R.M., Dunlop M.G., Aspirin‐induced activation of the NF‐kappaB signaling pathway: a novel mechanism for aspirin‐mediated apoptosis in colon cancer cells, FASEB J., 15: 1273–1275, 2001. [PubMed] [Google Scholar]

[b75] 75. Chan T.A., Morin P.J., Vogelstein B., Kinzler K.W., Mechanisms underlying nonsteroidal antiinflammatory drug‐mediated apoptosis, Proc. Natl. Acad. Sci. U.S.A., 95: 681–686, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b76] 76. He T.C., Chan T.A., Vogelstein B., Kinzler K.W., PPARdelta is an APC‐regulated target of nonsteroidal antiinflammatory drugs, Cell, 99: 335–345, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b77] 77. Jaradat M.S., Wongsud B., Phornchirasilp S., Rangwala S.M., Shams G., Sutton M., Romstedt K.J., Noonan D.J., Feller D.R., Activation of peroxisome proliferator‐activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin, Biochem. Pharmacol., 62: 1587–1595, 2001. [DOI] [PubMed] [Google Scholar]

[b78] 78. Badawi A.F., Badr M.Z., Chemoprevention of breast cancer by targeting cyclooxygenase‐2 and peroxisome proliferator‐activated receptor‐gamma (Review), Int. J. Oncol. 20: 1109–1122, 2002. [PubMed] [Google Scholar]

[b79] 79. Holford N.H.G., Benet L.Z., Pharmacokinetics and Pharmacodynamics: rational dose selection and the time course of drug action In: Katzung B.G., ed., Basic and Clincal Pharmacology. 6th edition, Appleton & Lange, Norwalk , Connecticut , 1995, pp 33–48. [Google Scholar]

[b80] 80. Koki A.T., Leahy K.M., Masferrer J.L., Potential utility of COX‐2 inhibitors in chemoprevention and chemotherapy. Expert Opin. Investig. Drugs 8: 1623–1638, 1999. [DOI] [PubMed] [Google Scholar]

[b81] 81. Sano H., Kawahito Y., Wilder R.L., Hashiramoto A., Mukai S., Asai K., Kimura S., Kato H., Kondo M., Hla T., Expression of cyclooxygenase‐1 and −2 in human colorectal cancer, Cancer Res., 55: 3785–3789, 1995. [PubMed] [Google Scholar]

[b82] 82. Molina M.A., Sitja‐Arnau M., Lemoine M.G., Frazier M.L., Sinicrope F.A., Increased cyclooxygenase‐2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti‐inflammatory drugs, Cancer Res., 59: 4356–4362, 1999. [PubMed] [Google Scholar]

[b83] 83. Ristimaki A., Honkanen N., Jankala H., Sipponen P., Harkonen M., Expression of cyclooxygenase‐2 in human gastric carcinoma, Cancer Res., 57: 1276–1280, 1997. [PubMed] [Google Scholar]

[b84] 84. Uefuji K., Ichikura T., Mochizuki H., Shinomiya N., Expression of cyclooxygenase‐2 protein in gastric adenocarcinoma, J. Surg. Oncol., 69: 168–172, 1998. [DOI] [PubMed] [Google Scholar]

[b85] 85. Tsujii M., DuBois R.N., Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2, Cell, 83: 493–50, 1995. [DOI] [PubMed] [Google Scholar]

[b86] 86. Oshima M., Dinchuk J.E., Kargman S.L., Oshima H., Hancock B., Kwong E., Trzaskos J.M., Evans J.F., Taketo M.M., Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX‐2), Cell, 87: 803–809, 1996. [DOI] [PubMed] [Google Scholar]

[b87] 87. Liu C.H., Chang S.H., Narko K., Trifan O.C., Wu M.T., Smith E., Haudenschild C., Lane T.F., Hla T., Overexpression of cyclooxygenase‐2 is sufficient to induce tumorigenesis in transgenic mice, J. Biol. Chem., 276: 18563–18569, 2001. [DOI] [PubMed] [Google Scholar]

[b88] 88. Kinoshita T., Takahashi Y., Sakashita T., Inoue H., Tanabe T., Yoshimoto T., Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells, Biochim. Biophys. Acta, 1438: 120–130, 1999. [DOI] [PubMed] [Google Scholar]

[b89] 89. Hashimoto N., Watanabe T., Ikeda Y., Yamada H., Taniguchi S., Mitsui H., Kurokawa K., Prostaglandins induce proliferation of rat hepatocytes through a prostaglandin E2 receptor EP3 subtype, Am. J. Physiol., 272: G597–G604, 1997. [DOI] [PubMed] [Google Scholar]

[b90] 90. Kimura M., Osumi S., Ogihara M., Prostaglandin E(2) (EP(1)) receptor agonist‐induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes: the involvement of TGF‐alpha, Endocrinology, 142: 4428–4440, 2001. [DOI] [PubMed] [Google Scholar]

[b91] 91. Pentland A.P., Needleman P., Modulation of keratinocyte proliferation in vitro by endogenous prostaglandin synthesis, J. Clin. Invest., 77: 246–251, 1986. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b92] 92. Bandyopadhyay G.K., Imagawa W., Wallace D., Nandi S., Linoleate metabolites enhance the in vitro proliferative response of mouse mammary epithelial cells to epidermal growth factor, J. Biol. Chem., 262: 2750–2756, 1987. [PubMed] [Google Scholar]

[b93] 93. Nolan R.D., Danilowicz R.M., Eling T.E., Role of arachidonic acid metabolism in the mitogenic response of BALB/c 3T3 fibroblasts to epidermal growth factor, Mol. Pharmacol., 33: 650–656, 1988. [PubMed] [Google Scholar]

[b94] 94. Quarles L.D., Haupt D.M., Davidai G., Middleton J.P., Prostaglandin F2 alpha‐induced mitogenesis in MC3T3‐E1 osteoblasts: role of protein kinase‐C‐mediated tyrosine phosphorylation, Endocrinology, 132: 1505–1513, 1993. [DOI] [PubMed] [Google Scholar]

[b95] 95. Goin M., Pignataro O., Jimenez de Asua L., Early cell cycle diacylglycerol (DAG) content and protein kinase C (PKC) activity enhancement potentiates prostaglandin F2 alpha (PGF2 alpha) induced mitogenesis in Swiss 3T3 cells, FEBS Lett., 316: 68–72, 1993. [DOI] [PubMed] [Google Scholar]

[b96] 96. Zhao Y., Agarwal V.R., Mendelson C.R., Simpson E.R., Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene, Endocrinology, 137: 5739–5742, 1996. [DOI] [PubMed] [Google Scholar]

[b97] 97. Harris R.E., Robertson F.M., Abou‐Issa H.M., Farrar W.B., Brueggemeier R., Genetic induction and upregulation of cyclooxygenase (COX) and aromatase (CYP19): an extension of the dietary fat hypothesis of breast cancer, Med. Hypotheses, 52: 291–292, 1999. [DOI] [PubMed] [Google Scholar]

[b98] 98. McKanna J.A., Zhang M.Z., Wang J.L., Cheng H., Harris R.C., Constitutive expression of cyclooxygenase 2 in rat vas deferens, Am. J. Physiol., 275: R227–R233, 1998. [DOI] [PubMed] [Google Scholar]

[b99] 99. Lyson K., Indomethacin suppression of the estradiol induced proliferative response of the seminal vesicles, Exp. Clin. Endocrinol., 84: 223–227, 1984. [PubMed] [Google Scholar]

[b100] 100. Fürstenberger G., Marks F., Indomethacin inhibition of cell proliferation induced by the phorbolester TPA is reversed by prostaglandin E2 in mouse epidermis in vivo, Biochem. Biophys. Res. Commun., 84: 1103–1111, 1978. [DOI] [PubMed] [Google Scholar]

[b101] 101. Verma A.K., Ashendel C.L., Boutwell R.K., Inhibition by prostaglandin synthesis inhibitors of the induction of epidermal ornithine decarboxylase activity, the accumulation of prostaglandins and tumor promotion caused by 12 O tetradecanoylphorbol 13 acetate, Cancer Res., 40: 308–315, 1980. [PubMed] [Google Scholar]

[b102] 102. Marnett L.J., Aspirin and the potential role of prostaglandins in colon cancer, Cancer Res., 52: 5575–5589, 1992. [PubMed] [Google Scholar]

[b103] 103. Sun Y., Tang X.M., Half E., Kuo M.T., Sinicrope F.A., Cyclooxygenase‐2 overexpression reduces apoptotic susceptibility by inhibiting the cytochrome c‐dependent apoptotic pathway in human colon cancer cells, Cancer Res., 62: 6323–6328, 2002. [PubMed] [Google Scholar]

[b104] 104. Ottonello L., Gonella R., Dapino P., Sacchetti C., Dallegri F., Prostaglandin E2 inhibits apoptosis in human neutrophilic polymorphonuclear leukocytes: role of intracellular cyclic AMP levels, Exp. Hematol., 26: 895–902, 1998. [PubMed] [Google Scholar]

[b105] 105. Kawamura T., Horie S., Maruyama T., Akira T., Imagawa T., Nakamura N., Prostaglandin E1 transported into cells blocks the apoptotic signals induced by nerve growth factor deprivation, J. Neurochem., 72: 1907–1914, 1999. [DOI] [PubMed] [Google Scholar]

[b106] 106. Kroll B., Kunz S., Tu N., Schwarz L.R., Inhibition of transforming growth factor‐beta1 and UV light‐induced apoptosis by prostanoids in primary cultures of rat hepatocytes, Toxicol. Appl. Pharmacol., 152: 240–250, 1998. [DOI] [PubMed] [Google Scholar]

[b107] 107. Kliewer S.A., Lenhard J.M., Willson T.M., Patel I., Morris D.C., Lehmann J.M., A prostaglandin J2 metabolite binds peroxisome proliferator‐activated receptor gamma and promotes adipocyte differentiation, Cell, 83: 813–819, 1995. [DOI] [PubMed] [Google Scholar]

[b108] 108. Fitzpatrick F.A., Wynalda M.A., Albumin‐catalyzed metabolism of prostaglandin D2, J. Biol. Chem., 258: 11713–11718, 1983. [PubMed] [Google Scholar]

[b109] 109. Demetri G.D., Fletcher C.D., Mueller E., Sarraf P., Naujoks R., Campbell N., Spiegelman B.M., Singer S., Induction of solid tumor differentiation by the peroxisome proliferator‐activated receptor‐gamma ligand troglitazone in patients with liposarcoma, Proc. Natl. Acad. Sci. U.S.A., 96: 3951–3956, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b110] 110. Clay C.E., Namen A.M., Fonteh A.N., Atsumi G., High K.P., Chilton F.H., 15‐deoxy‐Delta(12,14)PGJ(2) induces diverse biological responses via PPARgamma activation in cancer cells, Prostaglandins Other Lipid. Mediat., 62: 23–32, 2000. [DOI] [PubMed] [Google Scholar]

[b111] 111. Ricote M., Li A.C., Willson T.M., Kelly C.J., Glass C.K., The peroxisome proliferator‐activated receptorgamma is a negative regulator of macrophage activation, Nature, 391: 79–82, 1998. [DOI] [PubMed] [Google Scholar]

[b112] 112. Bishop‐Bailey D., and Hla T., Endothelial cell apoptosis induced by the peroxisome proliferator‐activated receptor (PPAR) ligand 15‐deoxy‐Delta12, 14‐prostaglandin J2, J. Biol. Chem., 274, 17042–17048, 1999. [DOI] [PubMed] [Google Scholar]

[b113] 113. Xin X., Yang S., Kowalski J., Gerritsen M.E., Peroxisome proliferator‐activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo, J. Biol. Chem., 274: 9116–9121, 1999. [DOI] [PubMed] [Google Scholar]

[b114] 114. Takashima T., Fujiwara Y., Higuchi K., Arakawa T., Yano Y., Hasuma T., Otani S., PPARgamma ligands inhibit growth of human esophageal adenocarcinoma cells through induction of apoptosis, cell cycle arrest and reduction of ornithine decarboxylase activity, Int. J. Oncol., 19: 465–471, 2001. [PubMed] [Google Scholar]

[b115] 115. Shimada T., Kojima K., Yoshiura K., Hiraishi H., Terano A., Characteristics of the peroxisome proliferator activated receptor gamma (PPARgamma) ligand induced apoptosis in colon cancer cells, Gut, 50: 658–64, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b116] 116. Girnun G.D., Smith W.M., Drori S., Sarraf P., Mueller E., Eng C., Nambiar P., Rosenberg D.W., Bronson R.T., Edelmann W., Kucherlapati R., Gonzalez F.J., Spiegelman B.M., APC‐dependent suppression of colon carcinogenesis by PPAR gamma, Proc. Natl. Acad. Sci. U.S.A., 99: 13771–13776, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b117] 117. Yamakawa K., Hosoi M., Koyama H., Tanaka S., Fukumoto S., Morii H., Nishizawa Y., Peroxisome proliferator‐activated receptor‐gamma agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells, Biochem. Biophys. Res. Commun., 271: 571–574, 2000. [DOI] [PubMed] [Google Scholar]

[b118] 118. Haslmayer P., Thalhammer T., Jager W., Aust S., Steiner G., Ensinger C., Obrist P., The peroxisome proliferator‐activated receptor gamma ligand 15‐deoxy‐Delta12,14‐prostaglandin J2 induces vascular endothelial growth factor in the hormone‐independent prostate cancer cell line PC 3 and the urinary bladder carcinoma cell line 5637, Int. J. Oncol., 21: 915–920, 2002. [PubMed] [Google Scholar]

[b119] 119. Bunting S., Gryglewski R., Moncada S., Vane J.R., Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which re‐laxes strips of mesenteric and coeliac ateries and inhibits platelet aggregation, Prostaglandins, 12: 897–913, 1976. [DOI] [PubMed] [Google Scholar]

[b120] 120. Whittle B.J., Moncada S., Whiting F., Vane J.R., Carbacyclin‐a potent stable prostacyclin analogue for the inhibition of platelet aggregation, Prostaglandins, 19: 605–627, 1980. [DOI] [PubMed] [Google Scholar]

[b121] 121. Baxter G.S., Clayton J.K., Coleman R.A., Marshall K., Sangha R., Senior J., Characterization of the prostanoid receptors mediating constriction and re‐laxation of human isolated uterine artery, Br. J. Pharmacol., 116: 1692–1696, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b122] 122. Lim H., Dey S.K., A novel pathway of prostacyclin signaling‐hanging out with nuclear receptors, Endocrinology, 143: 3207–3210, 2002. [DOI] [PubMed] [Google Scholar]

[b123] 123. Gupta R.A., Tan J., Krause W.F., Geraci M.W., Willson T.M., Dey S.K., DuBois R.N., Prostacyclin‐mediated activation of peroxisome proliferator‐activated receptor‐δ in colorectal cancer, Proc. Natl. Acad. Sci. U.S.A., 97: 13275–13280, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b124] 124. Roy, H. K. , Karolski, W. J. , Ratashak, A. , Distal bowel selectivity in the chemoprevention of experimental colon carcinogenesis by the non‐steroidal anti‐inflammatory drug nabumetone, Int. J. Cancer, 92: 609–615, 2001. [DOI] [PubMed] [Google Scholar]

[b125] 125. Tong B.J., Tan J., Tajeda L., Das S.K., Chapman J.A., DuBois R.N., Dey S.K., Heightened expression of cyclooxygenase‐2 and peroxisome proliferator‐activated receptor‐δ in human endometrial adenocarcinoma, Neoplasia, 2: 483–490, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b126] 126. Park, B. H. , Vogelstein, B. , Kinzler, K. W. , Genetic disruption of PPARδ decreases the tumorigenicity of human colon cancer cells, Proc. Natl. Acad. Sci. U.S.A., 98: 2598–2603, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b127] 127. Barak, Y. , Liao, D. , He, W. , Ong, E. S. , Nelson, M. C. , Olefsky, J. M. , Boland, R. , Evans, R. M. , Effects of peroxisome proliferator‐activated receptor‐δ on placentation, adiposity, and colorectal cancer, Proc. Natl. Acad. Sci. U.S.A., 99: 303–308, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b128] 128. Shao J., Sheng H., DuBois R.N., Peroxisome proliferatoractivated receptors modulate K‐Ras‐mediated transformation of intestinal epithelial cells, Cancer Res., 62: 3282–3288, 2002. [PubMed] [Google Scholar]

[b129] 129. Takahashi K., Sawasaki Y., Hata J., Mukai K., Goto T., Spontaneous transformation and immortalization of human endothelial cells, In Vitro Cell & Dev. Biol., 26: 265–274, 1990. [DOI] [PubMed] [Google Scholar]

[b130] 130. Brown J., Reading S.J., Jones S., Fitchett C.J., Howl J., Martin A., Longland C.L., Michelangeli F., Dubrova Y.E., Brown C.A., Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83, Lab. Invest., 80w: 37–45, 2000. [DOI] [PubMed] [Google Scholar]

[b131] 131. Narko K., Ristimaki A., MacPhee M., Smith E., Haudenschild C.C., Hla T., Tumorigenic transformation of immortalized ECV endothelial cells by cyclooxygenase‐1 overexpression, J. Biol. Chem., 272: 21455–21460, 1997. [DOI] [PubMed] [Google Scholar]

[b132] 132. No D., Yao T.P., Evans R.M., Ecdysone‐inducible gene expression in mammalian cells and transgenic mice, Proc. Natl. Acad. Sci. U.S.A., 93: 3346–3351, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b133] 133. Trifan O.C., Smith R.M., Thompson B.D., Hla T., Overexpression of cyclooxygenase‐2 induces cell‐cycle arrest: evidence for a prostaglandin‐independent mechanism, J Biol. Chem., 274: 34141–34147, 1999. [DOI] [PubMed] [Google Scholar]

[b134] 134. Lecomte, M. , Laneuville, O. , Ji, C. , DeWitt, D.L. , Smith, W.L. , Acetylation of human prostaglandin endoperoxide synthase‐2 (cyclooxygenase‐2) by aspirin, J. Biol. Chem., 269: 13207–13215, 1994. [PubMed] [Google Scholar]

[b135] 135. Zahner G., Wolf G., Ayoub M., Reinking R., Panzer U., Shankland S.J., Stahl R.A., Cyclooxygenase‐2 overexpression inhibits platelet‐derived growth factor‐induced mesangial cell proliferation through induction of the tumor suppressor gene p53 and the cyclin‐dependent kinase inhibitors p21waf‐1/cip‐1 and p27kip‐1, J. Biol. Chem., 277: 9763–9771, 2002. [DOI] [PubMed] [Google Scholar]

[b136] 136. DuBois R.N., Abramson S.B., Crofford L., Gupta R.A., Simon L.S., Van De Putte L.B., and Lipsky P.E., Cyclooxygenase in biology and disease, FASEB J 12: 1063–1073, 1998. [PubMed] [Google Scholar]

[b137] 137. Munroe, D.G. , Wang, E.Y. , MacIntyre, J.P. , Tam, S.S. , Lee, D.H. , Taylor, G.R. , Zhou, L. , Plante, R.K. , Kazmi, S.M. , Bauerle, P.A. , et al. Novel intracellular signaling function of prostaglandin H synthase‐1 in NF‐kappa B activation, J. Inflamm., 45: 260–268, 1995. [PubMed] [Google Scholar]

[b138] 138. Ballif B.A., Mincek N.V., Barratt J.T., Wilson M.L., Simmons D.L., Interaction of cyclooxygenases with an apoptosis‐ and autoimmunity‐associated protein, Proc. Natl. Acad. Sci. U.S.A., 93: 5544–5549, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b139] 139. Leahy, K.M. , Ornberg, R.L. , Wang, Y. , Zweifel, B.S. , Koki, A.T. , Masferrer J.L., Cyclooxygenase‐2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo , Cancer Res., 62: 625–31, 2002. [PubMed] [Google Scholar]

[b140] 140. Karim, A. , Boynton, J. , Wallemark, C. , Kent, J. , Frazier‐O'Bannon, L. , Effects of celecoxib (cyp2c9 substrate) and omeprazole (cyp2c9 substrate /inhibitor) on systemic exposure to each other, AAPS. Pharm. Sci., 3: T3669 (Abstr.), 2001. [Google Scholar]

PERMALINK

Cyclooxygenase‐2 modulates cellular growth and promotes tumorigenesis

O C Trifan

T Hla

Abstract

References

ACTIONS

PERMALINK

RESOURCES

Cite

Add to Collections

PERMALINK

Cyclooxygenase‐2 modulates cellular growth and promotes tumorigenesis

O C Trifan

T Hla

Abstract

References

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases