Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4 (original) (raw)

Abstract

Cyclin D1 plays an important role in the development of breast cancer and is required for normal breast cell proliferation and differentiation associated with pregnancy. We show that ectopic expression of cyclin D1 can stimulate the transcriptional activity of the estrogen receptor in the absence of estradiol and that this activity can be inhibited by 4-hydroxytamoxifen and ICI 182,780. Cyclin D1 can form a specific complex with the estrogen receptor. Stimulation of the estrogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4 activation. Cyclin D1 may manifest its oncogenic potential in breast cancer in part through binding to the estrogen receptor and activation of the transcriptional activity of the receptor.

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  1. Adnane J., Gaudray P., Simon M. P., Simony-Lafontaine J., Jeanteur P., Theillet C. Proto-oncogene amplification and human breast tumor phenotype. Oncogene. 1989 Nov;4(11):1389–1395. [PubMed] [Google Scholar]
  2. Albanese C., Johnson J., Watanabe G., Eklund N., Vu D., Arnold A., Pestell R. G. Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions. J Biol Chem. 1995 Oct 6;270(40):23589–23597. doi: 10.1074/jbc.270.40.23589. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Berns E. M., Klijn J. G., van Staveren I. L., Portengen H., Noordegraaf E., Foekens J. A. Prevalence of amplification of the oncogenes c-myc, HER2/neu, and int-2 in one thousand human breast tumours: correlation with steroid receptors. Eur J Cancer. 1992;28(2-3):697–700. doi: 10.1016/s0959-8049(05)80129-7. [DOI] [PubMed] [Google Scholar]
  5. Berry M., Metzger D., Chambon P. Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J. 1990 Sep;9(9):2811–2818. doi: 10.1002/j.1460-2075.1990.tb07469.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borg A., Sigurdsson H., Clark G. M., Fernö M., Fuqua S. A., Olsson H., Killander D., McGurie W. L. Association of INT2/HST1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis. Br J Cancer. 1991 Jan;63(1):136–142. doi: 10.1038/bjc.1991.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown M. Estrogen receptor molecular biology. Hematol Oncol Clin North Am. 1994 Feb;8(1):101–112. [PubMed] [Google Scholar]
  8. Buckley M. F., Sweeney K. J., Hamilton J. A., Sini R. L., Manning D. L., Nicholson R. I., deFazio A., Watts C. K., Musgrove E. A., Sutherland R. L. Expression and amplification of cyclin genes in human breast cancer. Oncogene. 1993 Aug;8(8):2127–2133. [PubMed] [Google Scholar]
  9. Bunone G., Briand P. A., Miksicek R. J., Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J. 1996 May 1;15(9):2174–2183. [PMC free article] [PubMed] [Google Scholar]
  10. Cavaillès V., Dauvois S., L'Horset F., Lopez G., Hoare S., Kushner P. J., Parker M. G. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 1995 Aug 1;14(15):3741–3751. doi: 10.1002/j.1460-2075.1995.tb00044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chakravarti D., LaMorte V. J., Nelson M. C., Nakajima T., Schulman I. G., Juguilon H., Montminy M., Evans R. M. Role of CBP/P300 in nuclear receptor signalling. Nature. 1996 Sep 5;383(6595):99–103. doi: 10.1038/383099a0. [DOI] [PubMed] [Google Scholar]
  12. Courjal F., Louason G., Speiser P., Katsaros D., Zeillinger R., Theillet C. Cyclin gene amplification and overexpression in breast and ovarian cancers: evidence for the selection of cyclin D1 in breast and cyclin E in ovarian tumors. Int J Cancer. 1996 Aug 22;69(4):247–253. doi: 10.1002/(SICI)1097-0215(19960822)69:4<247::AID-IJC1>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  13. Dowdy S. F., Hinds P. W., Louie K., Reed S. I., Arnold A., Weinberg R. A. Physical interaction of the retinoblastoma protein with human D cyclins. Cell. 1993 May 7;73(3):499–511. doi: 10.1016/0092-8674(93)90137-f. [DOI] [PubMed] [Google Scholar]
  14. Ewen M. E., Oliver C. J., Sluss H. K., Miller S. J., Peeper D. S. p53-dependent repression of CDK4 translation in TGF-beta-induced G1 cell-cycle arrest. Genes Dev. 1995 Jan 15;9(2):204–217. doi: 10.1101/gad.9.2.204. [DOI] [PubMed] [Google Scholar]
  15. Ewen M. E., Sluss H. K., Sherr C. J., Matsushime H., Kato J., Livingston D. M. Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell. 1993 May 7;73(3):487–497. doi: 10.1016/0092-8674(93)90136-e. [DOI] [PubMed] [Google Scholar]
  16. Fantl V., Richards M. A., Smith R., Lammie G. A., Johnstone G., Allen D., Gregory W., Peters G., Dickson C., Barnes D. M. Gene amplification on chromosome band 11q13 and oestrogen receptor status in breast cancer. Eur J Cancer. 1990 Apr;26(4):423–429. doi: 10.1016/0277-5379(90)90009-i. [DOI] [PubMed] [Google Scholar]
  17. Fantl V., Stamp G., Andrews A., Rosewell I., Dickson C. Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev. 1995 Oct 1;9(19):2364–2372. doi: 10.1101/gad.9.19.2364. [DOI] [PubMed] [Google Scholar]
  18. Fawell S. E., White R., Hoare S., Sydenham M., Page M., Parker M. G. Inhibition of estrogen receptor-DNA binding by the "pure" antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6883–6887. doi: 10.1073/pnas.87.17.6883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  21. Halachmi S., Marden E., Martin G., MacKay H., Abbondanza C., Brown M. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. Science. 1994 Jun 3;264(5164):1455–1458. doi: 10.1126/science.8197458. [DOI] [PubMed] [Google Scholar]
  22. Hall M., Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res. 1996;68:67–108. doi: 10.1016/s0065-230x(08)60352-8. [DOI] [PubMed] [Google Scholar]
  23. Hanstein B., Eckner R., DiRenzo J., Halachmi S., Liu H., Searcy B., Kurokawa R., Brown M. p300 is a component of an estrogen receptor coactivator complex. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11540–11545. doi: 10.1073/pnas.93.21.11540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hinds P. W., Dowdy S. F., Eaton E. N., Arnold A., Weinberg R. A. Function of a human cyclin gene as an oncogene. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):709–713. doi: 10.1073/pnas.91.2.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hinds P. W., Mittnacht S., Dulic V., Arnold A., Reed S. I., Weinberg R. A. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell. 1992 Sep 18;70(6):993–1006. doi: 10.1016/0092-8674(92)90249-c. [DOI] [PubMed] [Google Scholar]
  26. Hirai H., Sherr C. J. Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1. Mol Cell Biol. 1996 Nov;16(11):6457–6467. doi: 10.1128/mcb.16.11.6457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kaelin W. G., Jr, Pallas D. C., DeCaprio J. A., Kaye F. J., Livingston D. M. Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product. Cell. 1991 Feb 8;64(3):521–532. doi: 10.1016/0092-8674(91)90236-r. [DOI] [PubMed] [Google Scholar]
  28. Kamei Y., Xu L., Heinzel T., Torchia J., Kurokawa R., Gloss B., Lin S. C., Heyman R. A., Rose D. W., Glass C. K. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 1996 May 3;85(3):403–414. doi: 10.1016/s0092-8674(00)81118-6. [DOI] [PubMed] [Google Scholar]
  29. Kato J. Y., Sherr C. J. Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11513–11517. doi: 10.1073/pnas.90.24.11513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kato J., Matsushime H., Hiebert S. W., Ewen M. E., Sherr C. J. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993 Mar;7(3):331–342. doi: 10.1101/gad.7.3.331. [DOI] [PubMed] [Google Scholar]
  31. Kato S., Endoh H., Masuhiro Y., Kitamoto T., Uchiyama S., Sasaki H., Masushige S., Gotoh Y., Nishida E., Kawashima H. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 1995 Dec 1;270(5241):1491–1494. doi: 10.1126/science.270.5241.1491. [DOI] [PubMed] [Google Scholar]
  32. Kumar V., Green S., Stack G., Berry M., Jin J. R., Chambon P. Functional domains of the human estrogen receptor. Cell. 1987 Dec 24;51(6):941–951. doi: 10.1016/0092-8674(87)90581-2. [DOI] [PubMed] [Google Scholar]
  33. Lavoie J. N., L'Allemain G., Brunet A., Müller R., Pouysségur J. Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J Biol Chem. 1996 Aug 23;271(34):20608–20616. doi: 10.1074/jbc.271.34.20608. [DOI] [PubMed] [Google Scholar]
  34. Le Douarin B., Zechel C., Garnier J. M., Lutz Y., Tora L., Pierrat P., Heery D., Gronemeyer H., Chambon P., Losson R. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18. EMBO J. 1995 May 1;14(9):2020–2033. doi: 10.1002/j.1460-2075.1995.tb07194.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lee J. W., Ryan F., Swaffield J. C., Johnston S. A., Moore D. D. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. Nature. 1995 Mar 2;374(6517):91–94. doi: 10.1038/374091a0. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Lukas J., Bartkova J., Rohde M., Strauss M., Bartek J. Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells independently of cdk4 activity. Mol Cell Biol. 1995 May;15(5):2600–2611. doi: 10.1128/mcb.15.5.2600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Matsushime H., Quelle D. E., Shurtleff S. A., Shibuya M., Sherr C. J., Kato J. Y. D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol. 1994 Mar;14(3):2066–2076. doi: 10.1128/mcb.14.3.2066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Migliaccio A., Di Domenico M., Castoria G., de Falco A., Bontempo P., Nola E., Auricchio F. Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO J. 1996 Mar 15;15(6):1292–1300. [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Oñate S. A., Tsai S. Y., Tsai M. J., O'Malley B. W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 1995 Nov 24;270(5240):1354–1357. doi: 10.1126/science.270.5240.1354. [DOI] [PubMed] [Google Scholar]
  43. Peeper D. S., Upton T. M., Ladha M. H., Neuman E., Zalvide J., Bernards R., DeCaprio J. A., Ewen M. E. Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein. Nature. 1997 Mar 13;386(6621):177–181. doi: 10.1038/386177a0. [DOI] [PubMed] [Google Scholar]
  44. Schmidhauser C., Casperson G. F., Myers C. A., Sanzo K. T., Bolten S., Bissell M. J. A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression. Mol Biol Cell. 1992 Jun;3(6):699–709. doi: 10.1091/mbc.3.6.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sherr C. J. Cancer cell cycles. Science. 1996 Dec 6;274(5293):1672–1677. doi: 10.1126/science.274.5293.1672. [DOI] [PubMed] [Google Scholar]
  46. Sherr C. J. G1 phase progression: cycling on cue. Cell. 1994 Nov 18;79(4):551–555. doi: 10.1016/0092-8674(94)90540-1. [DOI] [PubMed] [Google Scholar]
  47. Sherr C. J. Mammalian G1 cyclins. Cell. 1993 Jun 18;73(6):1059–1065. doi: 10.1016/0092-8674(93)90636-5. [DOI] [PubMed] [Google Scholar]
  48. Sicinski P., Donaher J. L., Geng Y., Parker S. B., Gardner H., Park M. Y., Robker R. L., Richards J. S., McGinnis L. K., Biggers J. D. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature. 1996 Dec 5;384(6608):470–474. doi: 10.1038/384470a0. [DOI] [PubMed] [Google Scholar]
  49. Sicinski P., Donaher J. L., Parker S. B., Li T., Fazeli A., Gardner H., Haslam S. Z., Bronson R. T., Elledge S. J., Weinberg R. A. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell. 1995 Aug 25;82(4):621–630. doi: 10.1016/0092-8674(95)90034-9. [DOI] [PubMed] [Google Scholar]
  50. Stepanova L., Leng X., Parker S. B., Harper J. W. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. 1996 Jun 15;10(12):1491–1502. doi: 10.1101/gad.10.12.1491. [DOI] [PubMed] [Google Scholar]
  51. Tam S. W., Shay J. W., Pagano M. Differential expression and cell cycle regulation of the cyclin-dependent kinase 4 inhibitor p16Ink4. Cancer Res. 1994 Nov 15;54(22):5816–5820. [PubMed] [Google Scholar]
  52. 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]
  53. 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]
  54. Wilcken N. R., Sarcevic B., Musgrove E. A., Sutherland R. L. Differential effects of retinoids and antiestrogens on cell cycle progression and cell cycle regulatory genes in human breast cancer cells. Cell Growth Differ. 1996 Jan;7(1):65–74. [PubMed] [Google Scholar]
  55. Yao T. P., Ku G., Zhou N., Scully R., Livingston D. M. The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10626–10631. doi: 10.1073/pnas.93.20.10626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Zhuang Y., Katzenellenbogen B. S., Shapiro D. J. Estrogen receptor mutants which do not bind 17 beta-estradiol dimerize and bind to the estrogen response element in vivo. Mol Endocrinol. 1995 Apr;9(4):457–466. doi: 10.1210/mend.9.4.7659089. [DOI] [PubMed] [Google Scholar]
  57. 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]
  58. 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]
  59. vom Baur E., Zechel C., Heery D., Heine M. J., Garnier J. M., Vivat V., Le Douarin B., Gronemeyer H., Chambon P., Losson R. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1. EMBO J. 1996 Jan 2;15(1):110–124. [PMC free article] [PubMed] [Google Scholar]