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. 1989 Mar;80:209–220. doi: 10.1289/ehp.8980209

Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

A M Pfeifer 1, J F Lechner 1, T Masui 1, R R Reddel 1, G E Mark 1, C C Harris 1
PMCID: PMC1567613  PMID: 2538323

Abstract

The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor beta 1 (TGF-beta 1) and serum] and exogenous [e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells.

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Selected References

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  1. Barnes D., Sato G. Methods for growth of cultured cells in serum-free medium. Anal Biochem. 1980 Mar 1;102(2):255–270. doi: 10.1016/0003-2697(80)90151-7. [DOI] [PubMed] [Google Scholar]
  2. Bertolero F., Kaighn M. E., Camalier R. F., Saffiotti U. Effects of serum and serum-derived factors on growth and differentiation of mouse keratinocytes. In Vitro Cell Dev Biol. 1986 Jul;22(7):423–428. doi: 10.1007/BF02623533. [DOI] [PubMed] [Google Scholar]
  3. Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
  4. Blasi E., Mathieson B. J., Varesio L., Cleveland J. L., Borchert P. A., Rapp U. R. Selective immortalization of murine macrophages from fresh bone marrow by a raf/myc recombinant murine retrovirus. Nature. 1985 Dec 19;318(6047):667–670. doi: 10.1038/318667a0. [DOI] [PubMed] [Google Scholar]
  5. Bonner T. I., Kerby S. B., Sutrave P., Gunnell M. A., Mark G., Rapp U. R. Structure and biological activity of human homologs of the raf/mil oncogene. Mol Cell Biol. 1985 Jun;5(6):1400–1407. doi: 10.1128/mcb.5.6.1400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bos J. L., Fearon E. R., Hamilton S. R., Verlaan-de Vries M., van Boom J. H., van der Eb A. J., Vogelstein B. Prevalence of ras gene mutations in human colorectal cancers. 1987 May 28-Jun 3Nature. 327(6120):293–297. doi: 10.1038/327293a0. [DOI] [PubMed] [Google Scholar]
  7. Brash D. E., Mark G. E., Farrell M. P., Harris C. C. Overview of human cells in genetic research: altered phenotypes in human cells caused by transferred genes. Somat Cell Mol Genet. 1987 Jul;13(4):429–440. doi: 10.1007/BF01534944. [DOI] [PubMed] [Google Scholar]
  8. Brash D. E., Reddel R. R., Quanrud M., Yang K., Farrell M. P., Harris C. C. Strontium phosphate transfection of human cells in primary culture: stable expression of the simian virus 40 large-T-antigen gene in primary human bronchial epithelial cells. Mol Cell Biol. 1987 May;7(5):2031–2034. doi: 10.1128/mcb.7.5.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bravo R., Neuberg M., Burckhardt J., Almendral J., Wallich R., Müller R. Involvement of common and cell type-specific pathways in c-fos gene control: stable induction of cAMP in macrophages. Cell. 1987 Jan 30;48(2):251–260. doi: 10.1016/0092-8674(87)90428-4. [DOI] [PubMed] [Google Scholar]
  10. Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
  11. Cerutti P. A. Prooxidant states and tumor promotion. Science. 1985 Jan 25;227(4685):375–381. doi: 10.1126/science.2981433. [DOI] [PubMed] [Google Scholar]
  12. Cleveland J. L., Jansen H. W., Bister K., Fredrickson T. N., Morse H. C., 3rd, Ihle J. N., Rapp U. R. Interaction between Raf and Myc oncogenes in transformation in vivo and in vitro. J Cell Biochem. 1986;30(3):195–218. doi: 10.1002/jcb.240300303. [DOI] [PubMed] [Google Scholar]
  13. Cuttitta F., Carney D. N., Mulshine J., Moody T. W., Fedorko J., Fischler A., Minna J. D. Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. 1985 Aug 29-Sep 4Nature. 316(6031):823–826. doi: 10.1038/316823a0. [DOI] [PubMed] [Google Scholar]
  14. DeLeo V. A., Scheide S., Horlich H., Hanson D., Southern W., Harber L. C., Weinstein I. B. The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on phospholipid metabolism of human epidermal keratinocytes in culture. Carcinogenesis. 1986 Jun;7(6):937–942. doi: 10.1093/carcin/7.6.937. [DOI] [PubMed] [Google Scholar]
  15. Delclos K. B., Nagle D. S., Blumberg P. M. Specific binding of phorbol ester tumor promoters to mouse skin. Cell. 1980 Apr;19(4):1025–1032. doi: 10.1016/0092-8674(80)90093-8. [DOI] [PubMed] [Google Scholar]
  16. Derynck R., Goeddel D. V., Ullrich A., Gutterman J. U., Williams R. D., Bringman T. S., Berger W. H. Synthesis of messenger RNAs for transforming growth factors alpha and beta and the epidermal growth factor receptor by human tumors. Cancer Res. 1987 Feb 1;47(3):707–712. [PubMed] [Google Scholar]
  17. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  18. DiPaolo J. A., Casto B. C. Quantitative studies of in vitro morphological transformation of Syrian hamster cells by inorganic metal salts. Cancer Res. 1979 Mar;39(3):1008–1013. [PubMed] [Google Scholar]
  19. Dicker P., Rozengurt E. Synergistic stimulation of early events and DNA synthesis by phorbol esters, polypeptide growth factors, and retinoids in cultured fibroblasts. J Supramol Struct. 1979;11(1):79–93. doi: 10.1002/jss.400110109. [DOI] [PubMed] [Google Scholar]
  20. Dicker P., Rozengurt E. Tumour promoter induces proliferation of 3T6 cells in serum-free medium, as do polypeptide growth factors. Exp Cell Res. 1980 Dec;130(2):474–477. doi: 10.1016/0014-4827(80)90030-0. [DOI] [PubMed] [Google Scholar]
  21. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  22. Ebeling J. G., Vandenbark G. R., Kuhn L. J., Ganong B. R., Bell R. M., Niedel J. E. Diacylglycerols mimic phorbol diester induction of leukemic cell differentiation. Proc Natl Acad Sci U S A. 1985 Feb;82(3):815–819. doi: 10.1073/pnas.82.3.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Elgjo K., Hennings H., Clausen O. P. Altered growth kinetics precede calcium-induced differentiation in mouse epidermal cells. In Vitro Cell Dev Biol. 1986 Jun;22(6):332–336. doi: 10.1007/BF02623407. [DOI] [PubMed] [Google Scholar]
  24. Fischer S. M., Viaje A., Mills G. D., Wong E. W., Weeks C. E., Slaga T. J. The growth of cultured human foreskin keratinocytes is not stimulated by a tumor promoter. Carcinogenesis. 1984 Jan;5(1):109–112. doi: 10.1093/carcin/5.1.109. [DOI] [PubMed] [Google Scholar]
  25. Gatmaitan Z., Jefferson D. M., Ruiz-Opazo N., Biempica L., Arias I. M., Dudas G., Leinwand L. A., Reid L. M. Regulation of growth and differentiation of a rat hepatoma cell line by the synergistic interactions of hormones and collagenous substrata. J Cell Biol. 1983 Oct;97(4):1179–1190. doi: 10.1083/jcb.97.4.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Grafstrom R. C., Curren R. D., Yang L. L., Harris C. C. Genotoxicity of formaldehyde in cultured human bronchial fibroblasts. Science. 1985 Apr 5;228(4695):89–91. doi: 10.1126/science.3975633. [DOI] [PubMed] [Google Scholar]
  27. Graziano S. L., Cowan B. Y., Carney D. N., Bryke C. R., Mitter N. S., Johnson B. E., Mark G. E., Planas A. T., Catino J. J., Comis R. L. Small cell lung cancer cell line derived from a primary tumor with a characteristic deletion of 3p. Cancer Res. 1987 Apr 15;47(8):2148–2155. [PubMed] [Google Scholar]
  28. Green S., Walter P., Kumar V., Krust A., Bornert J. M., Argos P., Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13;320(6058):134–139. doi: 10.1038/320134a0. [DOI] [PubMed] [Google Scholar]
  29. Griep A. E., DeLuca H. F. Decreased c-myc expression is an early event in retinoic acid-induced differentiation of F9 teratocarcinoma cells. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5539–5543. doi: 10.1073/pnas.83.15.5539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hagag N., Halegoua S., Viola M. Inhibition of growth factor-induced differentiation of PC12 cells by microinjection of antibody to ras p21. Nature. 1986 Feb 20;319(6055):680–682. doi: 10.1038/319680a0. [DOI] [PubMed] [Google Scholar]
  31. Hammond S. L., Ham R. G., Stampfer M. R. Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5435–5439. doi: 10.1073/pnas.81.17.5435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Harris C. C., Willey J. C., Saladino A. J., Grafstrom R. C. Effects of tumor promoters, aldehydes, peroxides, and tobacco smoke condensate on growth and differentiation of cultured normal and transformed human bronchial cells. Carcinog Compr Surv. 1985;8:159–171. [PubMed] [Google Scholar]
  33. Harris C. C., Willey J. C., Saladino A. J., Grafstrom R. C. Effects of tumor promoters, aldehydes, peroxides, and tobacco smoke condensate on growth and differentiation of cultured normal and transformed human bronchial cells. Carcinog Compr Surv. 1985;8:159–171. [PubMed] [Google Scholar]
  34. Hawley-Nelson P., Stanley J. R., Schmidt J., Gullino M., Yuspa S. H. The tumor promoter, 12-O-tetradecanoylphorbol-13-acetate accelerates keratinocyte differentiation and stimulates growth of an unidentified cell type in cultured human epidermis. Exp Cell Res. 1982 Jan;137(1):155–167. doi: 10.1016/0014-4827(82)90017-9. [DOI] [PubMed] [Google Scholar]
  35. Hayashi I., Carr B. I. DNA synthesis in rat hepatocytes: inhibition by a platelet factor and stimulation by an endogenous factor. J Cell Physiol. 1985 Oct;125(1):82–90. doi: 10.1002/jcp.1041250111. [DOI] [PubMed] [Google Scholar]
  36. Hoffmann D., Hecht S. S., Wynder E. L. Tumor promoters and cocarcinogens in tobacco carcinogenesis. Environ Health Perspect. 1983 Apr;50:247–257. doi: 10.1289/ehp.8350247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Hoosein N. M., Brattain D. E., McKnight M. K., Levine A. E., Brattain M. G. Characterization of the inhibitory effects of transforming growth factor-beta on a human colon carcinoma cell line. Cancer Res. 1987 Jun 1;47(11):2950–2954. [PubMed] [Google Scholar]
  38. Jetten A. M., Shirley J. E., Stoner G. Regulation of proliferation and differentiation of respiratory tract epithelial cells by TGF beta. Exp Cell Res. 1986 Dec;167(2):539–549. doi: 10.1016/0014-4827(86)90193-x. [DOI] [PubMed] [Google Scholar]
  39. Johnson B. E., Ihde D. C., Makuch R. W., Gazdar A. F., Carney D. N., Oie H., Russell E., Nau M. M., Minna J. D. myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course. J Clin Invest. 1987 Jun;79(6):1629–1634. doi: 10.1172/JCI112999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Kasid U., Pfeifer A., Weichselbaum R. R., Dritschilo A., Mark G. E. The raf oncogene is associated with a radiation-resistant human laryngeal cancer. Science. 1987 Aug 28;237(4818):1039–1041. doi: 10.1126/science.3616625. [DOI] [PubMed] [Google Scholar]
  41. Kawamura H., Strickland J. E., Yuspa S. H. Association of resistance to terminal differentiation with initiation of carcinogenesis in adult mouse epidermal cells. Cancer Res. 1985 Jun;45(6):2748–2752. [PubMed] [Google Scholar]
  42. Kawamura H., Strickland J. E., Yuspa S. H. Association of resistance to terminal differentiation with initiation of carcinogenesis in adult mouse epidermal cells. Cancer Res. 1985 Jun;45(6):2748–2752. [PubMed] [Google Scholar]
  43. Ke Y., Reddel R. R., Gerwin B. I., Miyashita M., McMenamin M., Lechner J. F., Harris C. C. Human bronchial epithelial cells with integrated SV40 virus T antigen genes retain the ability to undergo squamous differentiation. Differentiation. 1988 Jun;38(1):60–66. doi: 10.1111/j.1432-0436.1988.tb00592.x. [DOI] [PubMed] [Google Scholar]
  44. Knabbe C., Lippman M. E., Wakefield L. M., Flanders K. C., Kasid A., Derynck R., Dickson R. B. Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell. 1987 Feb 13;48(3):417–428. doi: 10.1016/0092-8674(87)90193-0. [DOI] [PubMed] [Google Scholar]
  45. Krokan H., Grafstrom R. C., Sundqvist K., Esterbauer H., Harris C. C. Cytotoxicity, thiol depletion and inhibition of O6-methylguanine-DNA methyltransferase by various aldehydes in cultured human bronchial fibroblasts. Carcinogenesis. 1985 Dec;6(12):1755–1759. doi: 10.1093/carcin/6.12.1755. [DOI] [PubMed] [Google Scholar]
  46. Kruijer W., Schubert D., Verma I. M. Induction of the proto-oncogene fos by nerve growth factor. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7330–7334. doi: 10.1073/pnas.82.21.7330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Kurzrock R., Gallick G. E., Gutterman J. U. Differential expression of p21ras gene products among histological subtypes of fresh primary human lung tumors. Cancer Res. 1986 Mar;46(3):1530–1534. [PubMed] [Google Scholar]
  48. Lacal J. C., Aaronson S. A. Activation of ras p21 transforming properties associated with an increase in the release rate of bound guanine nucleotide. Mol Cell Biol. 1986 Dec;6(12):4214–4220. doi: 10.1128/mcb.6.12.4214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Lacal J. C., de la Peña P., Moscat J., Garcia-Barreno P., Anderson P. S., Aaronson S. A. Rapid stimulation of diacylglycerol production in Xenopus oocytes by microinjection of H-ras p21. Science. 1987 Oct 23;238(4826):533–536. doi: 10.1126/science.2821623. [DOI] [PubMed] [Google Scholar]
  50. Lechner J. F., Haugen A., McClendon I. A., Pettis E. W. Clonal growth of normal adult human bronchial epithelial cells in a serum-free medium. In Vitro. 1982 Jul;18(7):633–642. doi: 10.1007/BF02796396. [DOI] [PubMed] [Google Scholar]
  51. Lechner J. F., Haugen A., McClendon I. A., Shamsuddin A. M. Induction of squamous differentiation of normal human bronchial epithelial cells by small amounts of serum. Differentiation. 1984;25(3):229–237. doi: 10.1111/j.1432-0436.1984.tb01361.x. [DOI] [PubMed] [Google Scholar]
  52. Lechner J. F., Kaighn M. E. EGF growth promoting activity is neutralized by phorbol esters. Cell Biol Int Rep. 1980 Jan;4(1):23–28. doi: 10.1016/0309-1651(80)90005-3. [DOI] [PubMed] [Google Scholar]
  53. Lechner J. F., McClendon I. A., LaVeck M. A., Shamsuddin A. M., Harris C. C. Differential control by platelet factors of squamous differentiation in normal and malignant human bronchial epithelial cells. Cancer Res. 1983 Dec;43(12 Pt 1):5915–5921. [PubMed] [Google Scholar]
  54. Lee J., Mehta K., Blick M. B., Gutterman J. U., Lopez-Berestein G. Expression of c-fos, c-myb, and c-myc in human monocytes: correlation with monocytic differentiation. Blood. 1987 May;69(5):1542–1545. [PubMed] [Google Scholar]
  55. Maciag T., Nemore R. E., Weinstein R., Gilchrest B. A. An endocrine approach to the control of epidermal growth: serum-free cultivation of human keratinocytes. Science. 1981 Mar 27;211(4489):1452–1454. doi: 10.1126/science.6970413. [DOI] [PubMed] [Google Scholar]
  56. Mark G. E., Pfeifer A., Mann D. L., Harris C. C., Berman R., Pert C. B. raf protooncogene expression in neural and immune tissues. Adv Biochem Psychopharmacol. 1988;44:45–55. [PubMed] [Google Scholar]
  57. Massagué J. The TGF-beta family of growth and differentiation factors. Cell. 1987 May 22;49(4):437–438. doi: 10.1016/0092-8674(87)90443-0. [DOI] [PubMed] [Google Scholar]
  58. Masui T., Lechner J. F., Yoakum G. H., Willey J. C., Harris C. C. Growth and differentiation of normal and transformed human bronchial epithelial cells. J Cell Physiol Suppl. 1986;4:73–81. doi: 10.1002/jcp.1041290414. [DOI] [PubMed] [Google Scholar]
  59. Masui T., Wakefield L. M., Lechner J. F., LaVeck M. A., Sporn M. B., Harris C. C. Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2438–2442. doi: 10.1073/pnas.83.8.2438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Matsui T., Nakao Y., Koizumi T., Katakami Y., Fujita T. Inhibition of phorbol ester-induced phenotypic differentiation of HL-60 cells by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a protein kinase inhibitor. Cancer Res. 1986 Feb;46(2):583–587. [PubMed] [Google Scholar]
  61. McGrath C. M., Soule H. D. Calcium regulation of normal human mammary epithelial cell growth in culture. In Vitro. 1984 Aug;20(8):652–662. doi: 10.1007/BF02619616. [DOI] [PubMed] [Google Scholar]
  62. McMahon J. B., Richards W. L., del Campo A. A., Song M. K., Thorgeirsson S. S. Differential effects of transforming growth factor-beta on proliferation of normal and malignant rat liver epithelial cells in culture. Cancer Res. 1986 Sep;46(9):4665–4671. [PubMed] [Google Scholar]
  63. Müller R., Slamon D. J., Tremblay J. M., Cline M. J., Verma I. M. Differential expression of cellular oncogenes during pre- and postnatal development of the mouse. Nature. 1982 Oct 14;299(5884):640–644. doi: 10.1038/299640a0. [DOI] [PubMed] [Google Scholar]
  64. Nakagawa T., Mabry M., de Bustros A., Ihle J. N., Nelkin B. D., Baylin S. B. Introduction of v-Ha-ras oncogene induces differentiation of cultured human medullary thyroid carcinoma cells. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5923–5927. doi: 10.1073/pnas.84.16.5923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Nau M. M., Brooks B. J., Battey J., Sausville E., Gazdar A. F., Kirsch I. R., McBride O. W., Bertness V., Hollis G. F., Minna J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature. 1985 Nov 7;318(6041):69–73. doi: 10.1038/318069a0. [DOI] [PubMed] [Google Scholar]
  66. Nau M. M., Brooks B. J., Jr, Carney D. N., Gazdar A. F., Battey J. F., Sausville E. A., Minna J. D. Human small-cell lung cancers show amplification and expression of the N-myc gene. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1092–1096. doi: 10.1073/pnas.83.4.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Nishizuka Y. Perspectives on the role of protein kinase C in stimulus-response coupling. J Natl Cancer Inst. 1986 Mar;76(3):363–370. [PubMed] [Google Scholar]
  68. O'Connor-McCourt M. D., Wakefield L. M. Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin. J Biol Chem. 1987 Oct 15;262(29):14090–14099. [PubMed] [Google Scholar]
  69. Parkinson E. K. Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding. Br J Cancer. 1985 Oct;52(4):479–493. doi: 10.1038/bjc.1985.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Parkinson E. K., Emmerson A. The effects of tumour promoters on the multiplication and morphology of cultured human epidermal keratinocytes. Carcinogenesis. 1982;3(5):525–531. doi: 10.1093/carcin/3.5.525. [DOI] [PubMed] [Google Scholar]
  71. Pragnell I. B., Spandidos D. A., Wilkie N. M. Consequences of altered oncogene expression in rodent cells. Proc R Soc Lond B Biol Sci. 1985 Oct 22;226(1242):107–119. doi: 10.1098/rspb.1985.0085. [DOI] [PubMed] [Google Scholar]
  72. Reddel R. R., Ke Y., Gerwin B. I., McMenamin M. G., Lechner J. F., Su R. T., Brash D. E., Park J. B., Rhim J. S., Harris C. C. Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes. Cancer Res. 1988 Apr 1;48(7):1904–1909. [PubMed] [Google Scholar]
  73. Rheinwald J. G., Beckett M. A. Defective terminal differentiation in culture as a consistent and selectable character of malignant human keratinocytes. Cell. 1980 Nov;22(2 Pt 2):629–632. doi: 10.1016/0092-8674(80)90373-6. [DOI] [PubMed] [Google Scholar]
  74. Rice R. H., Green H. Relation of protein synthesis and transglutaminase activity to formation of the cross-linked envelope during terminal differentiation of the cultured human epidermal keratinocyte. J Cell Biol. 1978 Mar;76(3):705–711. doi: 10.1083/jcb.76.3.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Rizzino A. Appearance of high affinity receptors for type beta transforming growth factor during differentiation of murine embryonal carcinoma cells. Cancer Res. 1987 Aug 15;47(16):4386–4390. [PubMed] [Google Scholar]
  76. Rodenhuis S., van de Wetering M. L., Mooi W. J., Evers S. G., van Zandwijk N., Bos J. L. Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung. N Engl J Med. 1987 Oct 8;317(15):929–935. doi: 10.1056/NEJM198710083171504. [DOI] [PubMed] [Google Scholar]
  77. Rosenberg Y. J., Malek T. R., Schaeffer D. E., Santoro T. J., Mark G. E., Steinberg A. D., Mountz J. D. Unusual expression of IL 2 receptors and both the c-myb and c-raf oncogenes in T cell lines and clones derived from autoimmune MRL-lpr/lpr mice. J Immunol. 1985 May;134(5):3120–3123. [PubMed] [Google Scholar]
  78. Rosenthal A., Lindquist P. B., Bringman T. S., Goeddel D. V., Derynck R. Expression in rat fibroblasts of a human transforming growth factor-alpha cDNA results in transformation. Cell. 1986 Jul 18;46(2):301–309. doi: 10.1016/0092-8674(86)90747-6. [DOI] [PubMed] [Google Scholar]
  79. Sacks P. G., Parnes S. M., Price J. C., Risemberg H., Goldstein J. C., Marko M., Parsons D. F. In vitro modulation of differentiation by calcium in organ cultures of human and murine epithelial tissue. In Vitro Cell Dev Biol. 1985 Feb;21(2):99–107. doi: 10.1007/BF02620950. [DOI] [PubMed] [Google Scholar]
  80. Saladino A. J., Willey J. C., Lechner J. F., Grafstrom R. C., LaVeck M., Harris C. C. Effects of formaldehyde, acetaldehyde, benzoyl peroxide, and hydrogen peroxide on cultured normal human bronchial epithelial cells. Cancer Res. 1985 Jun;45(6):2522–2526. [PubMed] [Google Scholar]
  81. Salomon D. S., Perroteau I., Kidwell W. R., Tam J., Derynck R. Loss of growth responsiveness to epidermal growth factor and enhanced production of alpha-transforming growth factors in ras-transformed mouse mammary epithelial cells. J Cell Physiol. 1987 Mar;130(3):397–409. doi: 10.1002/jcp.1041300313. [DOI] [PubMed] [Google Scholar]
  82. Sasajima K., Willey J. C., Banks-Schlegel S. P., Harris C. C. Effects of tumor promoters and cocarcinogens on growth and differentiation of cultured human esophageal epithelial cells. J Natl Cancer Inst. 1987 Mar;78(3):419–423. [PubMed] [Google Scholar]
  83. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  84. Shimizu K., Nakatsu Y., Oh-uchida M., Nomoto S., Sekiguchi M. [Activated c-raf-1 gene from human stomach cancer]. Gan To Kagaku Ryoho. 1987 Jun;14(6 Pt 2):2140–2146. [PubMed] [Google Scholar]
  85. Sky-Peck H. H. Trace metals and neoplasia. Clin Physiol Biochem. 1986;4(1):99–111. [PubMed] [Google Scholar]
  86. Smits H. L., Floyd E. E., Jetten A. M. Molecular cloning of gene sequences regulated during squamous differentiation of tracheal epithelial cells and controlled by retinoic acid. Mol Cell Biol. 1987 Nov;7(11):4017–4023. doi: 10.1128/mcb.7.11.4017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Sporn M. B., Roberts A. B., Wakefield L. M., Assoian R. K. Transforming growth factor-beta: biological function and chemical structure. Science. 1986 Aug 1;233(4763):532–534. doi: 10.1126/science.3487831. [DOI] [PubMed] [Google Scholar]
  88. Stanley M. A., Crowcroft N. S., Quigley J. P., Parkinson E. K. Responses of human cervical keratinocytes in vitro to tumour promoters and diethylstilboestrol. Carcinogenesis. 1985 Jul;6(7):1011–1015. doi: 10.1093/carcin/6.7.1011. [DOI] [PubMed] [Google Scholar]
  89. Stanton V. P., Jr, Cooper G. M. Activation of human raf transforming genes by deletion of normal amino-terminal coding sequences. Mol Cell Biol. 1987 Mar;7(3):1171–1179. doi: 10.1128/mcb.7.3.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Tanaka T., Slamon D. J., Battifora H., Cline M. J. Expression of p21 ras oncoproteins in human cancers. Cancer Res. 1986 Mar;46(3):1465–1470. [PubMed] [Google Scholar]
  91. Teyssier J. R., Henry I., Dozier C., Ferre D., Adnet J. J., Pluot M. Recurrent deletion of the short arm of chromosome 3 in human renal cell carcinoma: shift of the c-raf 1 locus. J Natl Cancer Inst. 1986 Dec;77(6):1187–1195. [PubMed] [Google Scholar]
  92. Thiele C. J., Reynolds C. P., Israel M. A. Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma. 1985 Jan 31-Feb 6Nature. 313(6001):404–406. doi: 10.1038/313404a0. [DOI] [PubMed] [Google Scholar]
  93. Thomassen D. G., Saffiotti U., Kaighn M. E. Clonal proliferation of rat tracheal epithelial cells in serum-free medium and their responses to hormones, growth factors and carcinogens. Carcinogenesis. 1986 Dec;7(12):2033–2039. doi: 10.1093/carcin/7.12.2033. [DOI] [PubMed] [Google Scholar]
  94. Tsao M. C., Walthall B. J., Ham R. G. Clonal growth of normal human epidermal keratinocytes in a defined medium. J Cell Physiol. 1982 Feb;110(2):219–229. doi: 10.1002/jcp.1041100217. [DOI] [PubMed] [Google Scholar]
  95. Tucker R. F., Branum E. L., Shipley G. D., Ryan R. J., Moses H. L. Specific binding to cultured cells of 125I-labeled type beta transforming growth factor from human platelets. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6757–6761. doi: 10.1073/pnas.81.21.6757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Tucker R. F., Shipley G. D., Moses H. L., Holley R. W. Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science. 1984 Nov 9;226(4675):705–707. doi: 10.1126/science.6093254. [DOI] [PubMed] [Google Scholar]
  97. Tutton P. J., Barkla D. H. Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review). Anticancer Res. 1987 Jan-Feb;7(1):1–12. [PubMed] [Google Scholar]
  98. Umezawa K., Weinstein I. B., Horowitz A., Fujiki H., Matsushima T., Sugimura T. Similarity of teleocidin B and phorbol ester tumour promoters in effects on membrane receptors. Nature. 1981 Apr 2;290(5805):411–413. doi: 10.1038/290411a0. [DOI] [PubMed] [Google Scholar]
  99. Valenzuela D. M., Groffen J. Four human carcinoma cell lines with novel mutations in position 12 of c-K-ras oncogene. Nucleic Acids Res. 1986 Jan 24;14(2):843–852. doi: 10.1093/nar/14.2.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Verma I. M., Sassone-Corsi P. Proto-oncogene fos: complex but versatile regulation. Cell. 1987 Nov 20;51(4):513–514. doi: 10.1016/0092-8674(87)90115-2. [DOI] [PubMed] [Google Scholar]
  101. Wakefield L. M., Smith D. M., Masui T., Harris C. C., Sporn M. B. Distribution and modulation of the cellular receptor for transforming growth factor-beta. J Cell Biol. 1987 Aug;105(2):965–975. doi: 10.1083/jcb.105.2.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Wakefield L. M., Smith D. M., Masui T., Harris C. C., Sporn M. B. Distribution and modulation of the cellular receptor for transforming growth factor-beta. J Cell Biol. 1987 Aug;105(2):965–975. doi: 10.1083/jcb.105.2.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  104. Weinstein I. B. Growth factors, oncogenes, and multistage carcinogenesis. J Cell Biochem. 1987 Mar;33(3):213–224. doi: 10.1002/jcb.240330308. [DOI] [PubMed] [Google Scholar]
  105. Wier M. L., Scott R. E. Regulation of the terminal event in cellular differentiation: biological mechanisms of the loss of proliferative potential. J Cell Biol. 1986 May;102(5):1955–1964. doi: 10.1083/jcb.102.5.1955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Wille J. J., Jr, Maercklein P. B., Scott R. E. Neoplastic transformation and defective control of cell proliferation and differentiation. Cancer Res. 1982 Dec;42(12):5139–5146. [PubMed] [Google Scholar]
  107. Willey J. C., Grafstrom R. C., Moser C. E., Jr, Ozanne C., Sundquvist K., Harris C. C. Biochemical and morphological effects of cigarette smoke condensate and its fractions on normal human bronchial epithelial cells in vitro. Cancer Res. 1987 Apr 15;47(8):2045–2049. [PubMed] [Google Scholar]
  108. Willey J. C., Laveck M. A., McClendon I. A., Lechner J. F. Relationship of ornithine decarboxylase activity and cAMP metabolism to proliferation of normal human bronchial epithelial cells. J Cell Physiol. 1985 Aug;124(2):207–212. doi: 10.1002/jcp.1041240206. [DOI] [PubMed] [Google Scholar]
  109. Willey J. C., Moser C. E., Jr, Lechner J. F., Harris C. C. Differential effects of 12-O-tetradecanoylphorbol-13-acetate on cultured normal and neoplastic human bronchial epithelial cells. Cancer Res. 1984 Nov;44(11):5124–5126. [PubMed] [Google Scholar]
  110. Willey J. C., Moser C. E., Jr, Lechner J. F., Harris C. C. Differential effects of 12-O-tetradecanoylphorbol-13-acetate on cultured normal and neoplastic human bronchial epithelial cells. Cancer Res. 1984 Nov;44(11):5124–5126. [PubMed] [Google Scholar]
  111. Willey J. C., Saladino A. J., Ozanne C., Lechner J. F., Harris C. C. Acute effects of 12-O-tetradecanoylphorbol-13-acetate, teleocidin B, or 2,3,7,8-tetrachlorodibenzo-p-dioxin on cultured normal human bronchial epithelial cells. Carcinogenesis. 1984 Feb;5(2):209–215. doi: 10.1093/carcin/5.2.209. [DOI] [PubMed] [Google Scholar]
  112. Wong A. J., Ruppert J. M., Eggleston J., Hamilton S. R., Baylin S. B., Vogelstein B. Gene amplification of c-myc and N-myc in small cell carcinoma of the lung. Science. 1986 Jul 25;233(4762):461–464. doi: 10.1126/science.3014659. [DOI] [PubMed] [Google Scholar]
  113. Yoakum G. H., Lechner J. F., Gabrielson E. W., Korba B. E., Malan-Shibley L., Willey J. C., Valerio M. G., Shamsuddin A. M., Trump B. F., Harris C. C. Transformation of human bronchial epithelial cells transfected by Harvey ras oncogene. Science. 1985 Mar 8;227(4691):1174–1179. doi: 10.1126/science.3975607. [DOI] [PubMed] [Google Scholar]
  114. Yuasa Y., Srivastava S. K., Dunn C. Y., Rhim J. S., Reddy E. P., Aaronson S. A. Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene. Nature. 1983 Jun 30;303(5920):775–779. doi: 10.1038/303775a0. [DOI] [PubMed] [Google Scholar]
  115. Yuspa S. H., Morgan D. L. Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis. Nature. 1981 Sep 3;293(5827):72–74. doi: 10.1038/293072a0. [DOI] [PubMed] [Google Scholar]

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