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. 1998 Dec;51(6):305–309. doi: 10.1136/mp.51.6.305

Cell cycle regulators and their abnormalities in breast cancer.

P L Fernández 1, P Jares 1, M J Rey 1, E Campo 1, A Cardesa 1
PMCID: PMC395656  PMID: 10193510

Abstract

One of the main properties of cancer cells is their increased and deregulated proliferative activity. It is now well known that abnormalities in many positive and negative modulators of the cell cycle are frequent in many cancer types, including breast carcinomas. Abnormalities such as defective function of the retinoblastoma gene and cyclin-dependent kinase inhibitors (for example, p16, p21, and p27), as well as upregulation of cyclins, are often seen in breast tumours. These abnormalities are sometimes coincidental, and newly described interplays between them suggest the existence of a complex regulatory web in the cell cycle.

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Selected References

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  1. Altucci L., Addeo R., Cicatiello L., Dauvois S., Parker M. G., Truss M., Beato M., Sica V., Bresciani F., Weisz A. 17beta-Estradiol induces cyclin D1 gene transcription, p36D1-p34cdk4 complex activation and p105Rb phosphorylation during mitogenic stimulation of G(1)-arrested human breast cancer cells. Oncogene. 1996 Jun 6;12(11):2315–2324. [PubMed] [Google Scholar]
  2. Arnold A., Kim H. G., Gaz R. D., Eddy R. L., Fukushima Y., Byers M. G., Shows T. B., Kronenberg H. M. Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma. J Clin Invest. 1989 Jun;83(6):2034–2040. doi: 10.1172/JCI114114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbareschi M., Caffo O., Doglioni C., Fina P., Marchetti A., Buttitta F., Leek R., Morelli L., Leonardi E., Bevilacqua G. p21WAF1 immunohistochemical expression in breast carcinoma: correlations with clinicopathological data, oestrogen receptor status, MIB1 expression, p53 gene and protein alterations and relapse-free survival. Br J Cancer. 1996 Jul;74(2):208–215. doi: 10.1038/bjc.1996.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bartkova J., Lukas J., Müller H., Lützhøft D., Strauss M., Bartek J. Cyclin D1 protein expression and function in human breast cancer. Int J Cancer. 1994 May 1;57(3):353–361. doi: 10.1002/ijc.2910570311. [DOI] [PubMed] [Google Scholar]
  5. Bates S., Peters G. Cyclin D1 as a cellular proto-oncogene. Semin Cancer Biol. 1995 Apr;6(2):73–82. doi: 10.1006/scbi.1995.0010. [DOI] [PubMed] [Google Scholar]
  6. Borg A., Zhang Q. X., Alm P., Olsson H., Sellberg G. The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression. Cancer Res. 1992 May 15;52(10):2991–2994. [PubMed] [Google Scholar]
  7. Calvano J. E., Rush E. B., Tan L. K., Rosen P. P., Borgen P. I., Van Zee K. J. Absence of p16 gene (CDKN2) deletions in microdissected primary breast carcinoma specimens. Ann Surg Oncol. 1997 Jul-Aug;4(5):416–420. doi: 10.1007/BF02305555. [DOI] [PubMed] [Google Scholar]
  8. Catzavelos C., Bhattacharya N., Ung Y. C., Wilson J. A., Roncari L., Sandhu C., Shaw P., Yeger H., Morava-Protzner I., Kapusta L. Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer. Nat Med. 1997 Feb;3(2):227–230. doi: 10.1038/nm0297-227. [DOI] [PubMed] [Google Scholar]
  9. Chen X., Bargonetti J., Prives C. p53, through p21 (WAF1/CIP1), induces cyclin D1 synthesis. Cancer Res. 1995 Oct 1;55(19):4257–4263. [PubMed] [Google Scholar]
  10. Craig C., Wersto R., Kim M., Ohri E., Li Z., Katayose D., Lee S. J., Trepel J., Cowan K., Seth P. A recombinant adenovirus expressing p27Kip1 induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells. Oncogene. 1997 May 15;14(19):2283–2289. doi: 10.1038/sj.onc.1201064. [DOI] [PubMed] [Google Scholar]
  11. Dickson C., Fantl V., Gillett C., Brookes S., Bartek J., Smith R., Fisher C., Barnes D., Peters G. Amplification of chromosome band 11q13 and a role for cyclin D1 in human breast cancer. Cancer Lett. 1995 Mar 23;90(1):43–50. doi: 10.1016/0304-3835(94)03676-a. [DOI] [PubMed] [Google Scholar]
  12. Doglioni C., Pelosio P., Laurino L., Macri E., Meggiolaro E., Favretti F., Barbareschi M. p21/WAF1/CIP1 expression in normal mucosa and in adenomas and adenocarcinomas of the colon: its relationship with differentiation. J Pathol. 1996 Jul;179(3):248–253. doi: 10.1002/(SICI)1096-9896(199607)179:3<248::AID-PATH571>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  13. Dublin E. A., Patel N. K., Gillett C. E., Smith P., Peters G., Barnes D. M. Retinoblastoma and p16 proteins in mammary carcinoma: their relationship to cyclin D1 and histopathological parameters. Int J Cancer. 1998 Feb 20;79(1):71–75. doi: 10.1002/(sici)1097-0215(19980220)79:1<71::aid-ijc14>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  14. Fantl V., Smith R., Brookes S., Dickson C., Peters G. Chromosome 11q13 abnormalities in human breast cancer. Cancer Surv. 1993;18:77–94. [PubMed] [Google Scholar]
  15. Ferrando A. A., Balbín M., Pendás A. M., Vizoso F., Velasco G., López-Otín C. Mutational analysis of the human cyclin-dependent kinase inhibitor p27kip1 in primary breast carcinomas. Hum Genet. 1996 Jan;97(1):91–94. doi: 10.1007/BF00218840. [DOI] [PubMed] [Google Scholar]
  16. Foster S. A., Wong D. J., Barrett M. T., Galloway D. A. Inactivation of p16 in human mammary epithelial cells by CpG island methylation. Mol Cell Biol. 1998 Apr;18(4):1793–1801. doi: 10.1128/mcb.18.4.1793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fredersdorf S., Burns J., Milne A. M., Packham G., Fallis L., Gillett C. E., Royds J. A., Peston D., Hall P. A., Hanby A. M. High level expression of p27(kip1) and cyclin D1 in some human breast cancer cells: inverse correlation between the expression of p27(kip1) and degree of malignancy in human breast and colorectal cancers. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6380–6385. doi: 10.1073/pnas.94.12.6380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Geradts J., Wilson P. A. High frequency of aberrant p16(INK4A) expression in human breast cancer. Am J Pathol. 1996 Jul;149(1):15–20. [PMC free article] [PubMed] [Google Scholar]
  19. Gillett C. E., Lee A. H., Millis R. R., Barnes D. M. Cyclin D1 and associated proteins in mammary ductal carcinoma in situ and atypical ductal hyperplasia. J Pathol. 1998 Apr;184(4):396–400. doi: 10.1002/(SICI)1096-9896(199804)184:4<396::AID-PATH1259>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  20. Gillett C., Fantl V., Smith R., Fisher C., Bartek J., Dickson C., Barnes D., Peters G. Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res. 1994 Apr 1;54(7):1812–1817. [PubMed] [Google Scholar]
  21. Gray-Bablin J., Zalvide J., Fox M. P., Knickerbocker C. J., DeCaprio J. A., Keyomarsi K. Cyclin E, a redundant cyclin in breast cancer. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15215–15220. doi: 10.1073/pnas.93.26.15215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Graña X., Reddy E. P. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene. 1995 Jul 20;11(2):211–219. [PubMed] [Google Scholar]
  23. Hengst L., Reed S. I. Translational control of p27Kip1 accumulation during the cell cycle. Science. 1996 Mar 29;271(5257):1861–1864. doi: 10.1126/science.271.5257.1861. [DOI] [PubMed] [Google Scholar]
  24. Herman J. G., Merlo A., Mao L., Lapidus R. G., Issa J. P., Davidson N. E., Sidransky D., Baylin S. B. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 1995 Oct 15;55(20):4525–4530. [PubMed] [Google Scholar]
  25. Hunter T., Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994 Nov 18;79(4):573–582. doi: 10.1016/0092-8674(94)90543-6. [DOI] [PubMed] [Google Scholar]
  26. Jacks T., Weinberg R. A. The expanding role of cell cycle regulators. Science. 1998 May 15;280(5366):1035–1036. doi: 10.1126/science.280.5366.1035. [DOI] [PubMed] [Google Scholar]
  27. Jansen-Dürr P. How viral oncogenes make the cell cycle. Trends Genet. 1996 Jul;12(7):270–275. doi: 10.1016/0168-9525(96)81455-7. [DOI] [PubMed] [Google Scholar]
  28. Jares P., Rey M. J., Fernández P. L., Campo E., Nadal A., Muñoz M., Mallofré C., Muntané J., Nayach I., Estapé J. Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status. J Pathol. 1997 Jun;182(2):160–166. doi: 10.1002/(SICI)1096-9896(199706)182:2<160::AID-PATH814>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  29. Jiang M., Shao Z. M., Wu J., Lu J. S., Yu L. M., Yuan J. D., Han Q. X., Shen Z. Z., Fontana J. A. p21/waf1/cip1 and mdm-2 expression in breast carcinoma patients as related to prognosis. Int J Cancer. 1997 Oct 21;74(5):529–534. doi: 10.1002/(sici)1097-0215(19971021)74:5<529::aid-ijc9>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  30. Kamb A., Gruis N. A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S. V., Stockert E., Day R. S., 3rd, Johnson B. E., Skolnick M. H. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994 Apr 15;264(5157):436–440. doi: 10.1126/science.8153634. [DOI] [PubMed] [Google Scholar]
  31. Katayose Y., Kim M., Rakkar A. N., Li Z., Cowan K. H., Seth P. Promoting apoptosis: a novel activity associated with the cyclin-dependent kinase inhibitor p27. Cancer Res. 1997 Dec 15;57(24):5441–5445. [PubMed] [Google Scholar]
  32. Keyomarsi K., Conte D., Jr, Toyofuku W., Fox M. P. Deregulation of cyclin E in breast cancer. Oncogene. 1995 Sep 7;11(5):941–950. [PubMed] [Google Scholar]
  33. LaBaer J., Garrett M. D., Stevenson L. F., Slingerland J. M., Sandhu C., Chou H. S., Fattaey A., Harlow E. New functional activities for the p21 family of CDK inhibitors. Genes Dev. 1997 Apr 1;11(7):847–862. doi: 10.1101/gad.11.7.847. [DOI] [PubMed] [Google Scholar]
  34. Landberg G., Roos G. The cell cycle in breast cancer. APMIS. 1997 Aug;105(8):575–589. doi: 10.1111/j.1699-0463.1997.tb05056.x. [DOI] [PubMed] [Google Scholar]
  35. Li R., Waga S., Hannon G. J., Beach D., Stillman B. Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature. 1994 Oct 6;371(6497):534–537. doi: 10.1038/371534a0. [DOI] [PubMed] [Google Scholar]
  36. Li Y., Nichols M. A., Shay J. W., Xiong Y. Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb. Cancer Res. 1994 Dec 1;54(23):6078–6082. [PubMed] [Google Scholar]
  37. Loda M., Cukor B., Tam S. W., Lavin P., Fiorentino M., Draetta G. F., Jessup J. M., Pagano M. Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med. 1997 Feb;3(2):231–234. doi: 10.1038/nm0297-231. [DOI] [PubMed] [Google Scholar]
  38. Lovec H., Sewing A., Lucibello F. C., Müller R., Möröy T. Oncogenic activity of cyclin D1 revealed through cooperation with Ha-ras: link between cell cycle control and malignant transformation. Oncogene. 1994 Jan;9(1):323–326. [PubMed] [Google Scholar]
  39. Lukas J., Aagaard L., Strauss M., Bartek J. Oncogenic aberrations of p16INK4/CDKN2 and cyclin D1 cooperate to deregulate G1 control. Cancer Res. 1995 Nov 1;55(21):4818–4823. [PubMed] [Google Scholar]
  40. Lukas J., Müller H., Bartkova J., Spitkovsky D., Kjerulff A. A., Jansen-Dürr P., Strauss M., Bartek J. DNA tumor virus oncoproteins and retinoblastoma gene mutations share the ability to relieve the cell's requirement for cyclin D1 function in G1. J Cell Biol. 1994 May;125(3):625–638. doi: 10.1083/jcb.125.3.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lundberg A. S., Weinberg R. A. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol. 1998 Feb;18(2):753–761. doi: 10.1128/mcb.18.2.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. McIntosh G. G., Anderson J. J., Milton I., Steward M., Parr A. H., Thomas M. D., Henry J. A., Angus B., Lennard T. W., Horne C. H. Determination of the prognostic value of cyclin D1 overexpression in breast cancer. Oncogene. 1995 Sep 7;11(5):885–891. [PubMed] [Google Scholar]
  43. Michalides R., Hageman P., van Tinteren H., Houben L., Wientjens E., Klompmaker R., Peterse J. A clinicopathological study on overexpression of cyclin D1 and of p53 in a series of 248 patients with operable breast cancer. Br J Cancer. 1996 Mar;73(6):728–734. doi: 10.1038/bjc.1996.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Musgrove E. A., Hamilton J. A., Lee C. S., Sweeney K. J., Watts C. K., Sutherland R. L. Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression. Mol Cell Biol. 1993 Jun;13(6):3577–3587. doi: 10.1128/mcb.13.6.3577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Musgrove E. A., Lilischkis R., Cornish A. L., Lee C. S., Setlur V., Seshadri R., Sutherland R. L. Expression of the cyclin-dependent kinase inhibitors p16INK4, p15INK4B and p21WAF1/CIP1 in human breast cancer. Int J Cancer. 1995 Nov 15;63(4):584–591. doi: 10.1002/ijc.2910630420. [DOI] [PubMed] [Google Scholar]
  46. Müller H., Lukas J., Schneider A., Warthoe P., Bartek J., Eilers M., Strauss M. Cyclin D1 expression is regulated by the retinoblastoma protein. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2945–2949. doi: 10.1073/pnas.91.8.2945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Nadal A., Jares P., Cazorla M., Fernández P. L., Sanjuan X., Hernandez L., Pinyol M., Aldea M., Mallofré C., Muntané J. p21WAF1/Cip1 expression is associated with cell differentiation but not with p53 mutations in squamous cell carcinomas of the larynx. J Pathol. 1997 Oct;183(2):156–163. doi: 10.1002/(SICI)1096-9896(199710)183:2<156::AID-PATH908>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
  48. Nielsen N. H., Arnerlöv C., Emdin S. O., Landberg G. Cyclin E overexpression, a negative prognostic factor in breast cancer with strong correlation to oestrogen receptor status. Br J Cancer. 1996 Sep;74(6):874–880. doi: 10.1038/bjc.1996.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Nielsen N. H., Emdin S. O., Cajander J., Landberg G. Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein. Oncogene. 1997 Jan 23;14(3):295–304. doi: 10.1038/sj.onc.1200833. [DOI] [PubMed] [Google Scholar]
  50. Nobori T., Miura K., Wu D. J., Lois A., Takabayashi K., Carson D. A. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994 Apr 21;368(6473):753–756. doi: 10.1038/368753a0. [DOI] [PubMed] [Google Scholar]
  51. Pacilio C., Germano D., Addeo R., Altucci L., Petrizzi V. B., Cancemi M., Cicatiello L., Salzano S., Lallemand F., Michalides R. J. Constitutive overexpression of cyclin D1 does not prevent inhibition of hormone-responsive human breast cancer cell growth by antiestrogens. Cancer Res. 1998 Mar 1;58(5):871–876. [PubMed] [Google Scholar]
  52. Pelosio P., Barbareschi M., Bonoldi E., Marchetti A., Verderio P., Caffo O., Bevilacqua P., Boracchi P., Buttitta F., Barbazza R. Clinical significance of cyclin D1 expression in patients with node-positive breast carcinoma treated with adjuvant therapy. Ann Oncol. 1996 Sep;7(7):695–703. doi: 10.1093/oxfordjournals.annonc.a010718. [DOI] [PubMed] [Google Scholar]
  53. Ponce-Castañeda M. V., Lee M. H., Latres E., Polyak K., Lacombe L., Montgomery K., Mathew S., Krauter K., Sheinfeld J., Massague J. p27Kip1: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors. Cancer Res. 1995 Mar 15;55(6):1211–1214. [PubMed] [Google Scholar]
  54. Prall O. W., Sarcevic B., Musgrove E. A., Watts C. K., Sutherland R. L. Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. J Biol Chem. 1997 Apr 18;272(16):10882–10894. doi: 10.1074/jbc.272.16.10882. [DOI] [PubMed] [Google Scholar]
  55. Rey M. J., Fernández P. L., Jares P., Muñoz M., Nadal A., Peiró N., Nayach I., Mallofré C., Muntané J., Campo E. p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma. J Pathol. 1998 Mar;184(3):265–271. doi: 10.1002/(SICI)1096-9896(199803)184:3<265::AID-PATH8>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  56. Rosenberg C. L., Wong E., Petty E. M., Bale A. E., Tsujimoto Y., Harris N. L., Arnold A. PRAD1, a candidate BCL1 oncogene: mapping and expression in centrocytic lymphoma. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9638–9642. doi: 10.1073/pnas.88.21.9638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Schuuring E., Verhoeven E., van Tinteren H., Peterse J. L., Nunnink B., Thunnissen F. B., Devilee P., Cornelisse C. J., van de Vijver M. J., Mooi W. J. Amplification of genes within the chromosome 11q13 region is indicative of poor prognosis in patients with operable breast cancer. Cancer Res. 1992 Oct 1;52(19):5229–5234. [PubMed] [Google Scholar]
  58. Serrano M., Hannon G. J., Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993 Dec 16;366(6456):704–707. doi: 10.1038/366704a0. [DOI] [PubMed] [Google Scholar]
  59. Sgambato A., Han E. K., Zhou P., Schieren I., Weinstein I. B. Overexpression of cyclin E in the HC11 mouse mammary epithelial cell line is associated with growth inhibition and increased expression of p27(Kip1). Cancer Res. 1996 Mar 15;56(6):1389–1399. [PubMed] [Google Scholar]
  60. Sherr C. J., Roberts J. M. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995 May 15;9(10):1149–1163. doi: 10.1101/gad.9.10.1149. [DOI] [PubMed] [Google Scholar]
  61. Simpson J. F., Quan D. E., O'Malley F., Odom-Maryon T., Clarke P. E. Amplification of CCND1 and expression of its protein product, cyclin D1, in ductal carcinoma in situ of the breast. Am J Pathol. 1997 Jul;151(1):161–168. [PMC free article] [PubMed] [Google Scholar]
  62. Somasundaram K., Zhang H., Zeng Y. X., Houvras Y., Peng Y., Zhang H., Wu G. S., Licht J. D., Weber B. L., El-Deiry W. S. Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAF1/CiP1. Nature. 1997 Sep 11;389(6647):187–190. doi: 10.1038/38291. [DOI] [PubMed] [Google Scholar]
  63. Sutherland R. L., Watts C. K., Musgrove E. A. Cyclin gene expression and growth control in normal and neoplastic human breast epithelium. J Steroid Biochem Mol Biol. 1993 Dec;47(1-6):99–106. doi: 10.1016/0960-0760(93)90062-2. [DOI] [PubMed] [Google Scholar]
  64. Tan P., Cady B., Wanner M., Worland P., Cukor B., Magi-Galluzzi C., Lavin P., Draetta G., Pagano M., Loda M. The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. Cancer Res. 1997 Apr 1;57(7):1259–1263. [PubMed] [Google Scholar]
  65. Trudel M., Mulligan L., Cavenee W., Margolese R., Côté J., Gariépy G. Retinoblastoma and p53 gene product expression in breast carcinoma: immunohistochemical analysis and clinicopathologic correlation. Hum Pathol. 1992 Dec;23(12):1388–1394. doi: 10.1016/0046-8177(92)90059-c. [DOI] [PubMed] [Google Scholar]
  66. Van Zee K. J., Calvano J. E., Bisogna M. Hypomethylation and increased gene expression of p16INK4a in primary and metastatic breast carcinoma as compared to normal breast tissue. Oncogene. 1998 May 28;16(21):2723–2727. doi: 10.1038/sj.onc.1201794. [DOI] [PubMed] [Google Scholar]
  67. Wakasugi E., Kobayashi T., Tamaki Y., Nakano Y., Ito Y., Miyashiro I., Komoike Y., Miyazaki M., Takeda T., Monden T. Analysis of phosphorylation of pRB and its regulatory proteins in breast cancer. J Clin Pathol. 1997 May;50(5):407–412. doi: 10.1136/jcp.50.5.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wang T. C., Cardiff R. D., Zukerberg L., Lees E., Arnold A., Schmidt E. V. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature. 1994 Jun 23;369(6482):669–671. doi: 10.1038/369669a0. [DOI] [PubMed] [Google Scholar]
  69. Watts C. K., Brady A., Sarcevic B., deFazio A., Musgrove E. A., Sutherland R. L. Antiestrogen inhibition of cell cycle progression in breast cancer cells in associated with inhibition of cyclin-dependent kinase activity and decreased retinoblastoma protein phosphorylation. Mol Endocrinol. 1995 Dec;9(12):1804–1813. doi: 10.1210/mend.9.12.8614416. [DOI] [PubMed] [Google Scholar]
  70. Weinberg R. A. The retinoblastoma protein and cell cycle control. Cell. 1995 May 5;81(3):323–330. doi: 10.1016/0092-8674(95)90385-2. [DOI] [PubMed] [Google Scholar]
  71. Weinstat-Saslow D., Merino M. J., Manrow R. E., Lawrence J. A., Bluth R. F., Wittenbel K. D., Simpson J. F., Page D. L., Steeg P. S. Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions. Nat Med. 1995 Dec;1(12):1257–1260. doi: 10.1038/nm1295-1257. [DOI] [PubMed] [Google Scholar]
  72. Xu L., Sgroi D., Sterner C. J., Beauchamp R. L., Pinney D. M., Keel S., Ueki K., Rutter J. L., Buckler A. J., Louis D. N. Mutational analysis of CDKN2 (MTS1/p16ink4) in human breast carcinomas. Cancer Res. 1994 Oct 15;54(20):5262–5264. [PubMed] [Google Scholar]
  73. Zhang S. Y., Caamano J., Cooper F., Guo X., Klein-Szanto A. J. Immunohistochemistry of cyclin D1 in human breast cancer. Am J Clin Pathol. 1994 Nov;102(5):695–698. doi: 10.1093/ajcp/102.5.695. [DOI] [PubMed] [Google Scholar]
  74. Zukerberg L. R., Yang W. I., Gadd M., Thor A. D., Koerner F. C., Schmidt E. V., Arnold A. Cyclin D1 (PRAD1) protein expression in breast cancer: approximately one-third of infiltrating mammary carcinomas show overexpression of the cyclin D1 oncogene. Mod Pathol. 1995 Jun;8(5):560–567. [PubMed] [Google Scholar]
  75. Zwijsen R. M., Wientjens E., Klompmaker R., van der Sman J., Bernards R., Michalides R. J. CDK-independent activation of estrogen receptor by cyclin D1. Cell. 1997 Feb 7;88(3):405–415. doi: 10.1016/s0092-8674(00)81879-6. [DOI] [PubMed] [Google Scholar]
  76. el-Deiry W. S., Tokino T., Velculescu V. E., Levy D. B., Parsons R., Trent J. M., Lin D., Mercer W. E., Kinzler K. W., Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 Nov 19;75(4):817–825. doi: 10.1016/0092-8674(93)90500-p. [DOI] [PubMed] [Google Scholar]
  77. van Diest P. J., Michalides R. J., Jannink L., van der Valk P., Peterse H. L., de Jong J. S., Meijer C. J., Baak J. P. Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value. Am J Pathol. 1997 Feb;150(2):705–711. [PMC free article] [PubMed] [Google Scholar]

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