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Mol Cell Biol. 1997 September; 17(9): 5338–5347.
PMCID: PMC232384

Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4.

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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Selected References

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  • Adnane J, Gaudray P, Simon MP, Simony-Lafontaine J, Jeanteur P, Theillet C. Proto-oncogene amplification and human breast tumor phenotype. Oncogene. 1989 Nov;4(11):1389–1395. [PubMed]
  • Albanese C, Johnson J, Watanabe G, Eklund N, Vu D, Arnold A, Pestell RG. 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. [PubMed]
  • 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. [PubMed]
  • Berns EM, Klijn JG, van Staveren IL, Portengen H, Noordegraaf E, Foekens JA. 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. [PubMed]
  • 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. [PubMed]
  • Borg A, Sigurdsson H, Clark GM, Fernö M, Fuqua SA, Olsson H, Killander D, McGurie WL. 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. [PMC free article] [PubMed]
  • Brown M. Estrogen receptor molecular biology. Hematol Oncol Clin North Am. 1994 Feb;8(1):101–112. [PubMed]
  • Buckley MF, Sweeney KJ, Hamilton JA, Sini RL, Manning DL, Nicholson RI, deFazio A, Watts CK, Musgrove EA, Sutherland RL. Expression and amplification of cyclin genes in human breast cancer. Oncogene. 1993 Aug;8(8):2127–2133. [PubMed]
  • Bunone G, Briand PA, Miksicek RJ, 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. [PubMed]
  • Cavaillès V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ, Parker MG. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 1995 Aug 1;14(15):3741–3751. [PubMed]
  • Chakravarti D, LaMorte VJ, Nelson MC, Nakajima T, Schulman IG, Juguilon H, Montminy M, Evans RM. Role of CBP/P300 in nuclear receptor signalling. Nature. 1996 Sep 5;383(6595):99–103. [PubMed]
  • 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. [PubMed]
  • Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg RA. Physical interaction of the retinoblastoma protein with human D cyclins. Cell. 1993 May 7;73(3):499–511. [PubMed]
  • Ewen ME, Oliver CJ, Sluss HK, Miller SJ, Peeper DS. p53-dependent repression of CDK4 translation in TGF-beta-induced G1 cell-cycle arrest. Genes Dev. 1995 Jan 15;9(2):204–217. [PubMed]
  • Ewen ME, Sluss HK, Sherr CJ, Matsushime H, Kato J, Livingston DM. Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell. 1993 May 7;73(3):487–497. [PubMed]
  • Fantl V, Richards MA, Smith R, Lammie GA, Johnstone G, Allen D, Gregory W, Peters G, Dickson C, Barnes DM. Gene amplification on chromosome band 11q13 and oestrogen receptor status in breast cancer. Eur J Cancer. 1990 Apr;26(4):423–429. [PubMed]
  • 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. [PubMed]
  • Fawell SE, White R, Hoare S, Sydenham M, Page M, Parker MG. 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. [PubMed]
  • 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]
  • Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. [PubMed]
  • 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. [PubMed]
  • Hall M, Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res. 1996;68:67–108. [PubMed]
  • 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. [PubMed]
  • Hinds PW, Dowdy SF, Eaton EN, Arnold A, Weinberg RA. Function of a human cyclin gene as an oncogene. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):709–713. [PubMed]
  • Hinds PW, Mittnacht S, Dulic V, Arnold A, Reed SI, Weinberg RA. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell. 1992 Sep 18;70(6):993–1006. [PubMed]
  • Hirai H, Sherr CJ. Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1. Mol Cell Biol. 1996 Nov;16(11):6457–6467. [PMC free article] [PubMed]
  • Kaelin WG, Jr, Pallas DC, DeCaprio JA, Kaye FJ, Livingston DM. 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. [PubMed]
  • Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK, et al. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 1996 May 3;85(3):403–414. [PubMed]
  • Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. 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. [PubMed]
  • Kato JY, Sherr CJ. 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. [PubMed]
  • Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 1995 Dec 1;270(5241):1491–1494. [PubMed]
  • Kumar V, Green S, Stack G, Berry M, Jin JR, Chambon P. Functional domains of the human estrogen receptor. Cell. 1987 Dec 24;51(6):941–951. [PubMed]
  • Lavoie JN, 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. [PubMed]
  • Le Douarin B, Zechel C, Garnier JM, 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. [PubMed]
  • Lee JW, Ryan F, Swaffield JC, Johnston SA, Moore DD. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. Nature. 1995 Mar 2;374(6517):91–94. [PubMed]
  • Lovec H, Sewing A, Lucibello FC, 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]
  • 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. [PMC free article] [PubMed]
  • Matsushime H, Quelle DE, Shurtleff SA, Shibuya M, Sherr CJ, Kato JY. D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol. 1994 Mar;14(3):2066–2076. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Musgrove EA, Hamilton JA, Lee CS, Sweeney KJ, Watts CK, Sutherland RL. 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. [PMC free article] [PubMed]
  • Oñate SA, Tsai SY, Tsai MJ, O'Malley BW. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 1995 Nov 24;270(5240):1354–1357. [PubMed]
  • Peeper DS, Upton TM, Ladha MH, Neuman E, Zalvide J, Bernards R, DeCaprio JA, Ewen ME. Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein. Nature. 1997 Mar 13;386(6621):177–181. [PubMed]
  • Schmidhauser C, Casperson GF, Myers CA, Sanzo KT, Bolten S, Bissell MJ. 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. [PMC free article] [PubMed]
  • Sherr CJ. Mammalian G1 cyclins. Cell. 1993 Jun 18;73(6):1059–1065. [PubMed]
  • Sherr CJ. G1 phase progression: cycling on cue. Cell. 1994 Nov 18;79(4):551–555. [PubMed]
  • Sherr CJ. Cancer cell cycles. Science. 1996 Dec 6;274(5293):1672–1677. [PubMed]
  • Sicinski P, Donaher JL, Geng Y, Parker SB, Gardner H, Park MY, Robker RL, Richards JS, McGinnis LK, Biggers JD, et al. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature. 1996 Dec 5;384(6608):470–474. [PubMed]
  • Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ, Weinberg RA. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell. 1995 Aug 25;82(4):621–630. [PubMed]
  • Stepanova L, Leng X, Parker SB, Harper JW. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. 1996 Jun 15;10(12):1491–1502. [PubMed]
  • Tam SW, Shay JW, 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]
  • vom Baur E, Zechel C, Heery D, Heine MJ, Garnier JM, 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. [PubMed]
  • Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature. 1994 Jun 23;369(6482):669–671. [PubMed]
  • Weinstat-Saslow D, Merino MJ, Manrow RE, Lawrence JA, Bluth RF, Wittenbel KD, Simpson JF, Page DL, Steeg PS. Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions. Nat Med. 1995 Dec;1(12):1257–1260. [PubMed]
  • Wilcken NR, Sarcevic B, Musgrove EA, Sutherland RL. 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]
  • Yao TP, Ku G, Zhou N, Scully R, Livingston DM. 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. [PubMed]
  • Zhuang Y, Katzenellenbogen BS, Shapiro DJ. 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. [PubMed]
  • Zukerberg LR, Yang WI, Gadd M, Thor AD, Koerner FC, Schmidt EV, 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]
  • Zwijsen RM, Wientjens E, Klompmaker R, van der Sman J, Bernards R, Michalides RJ. CDK-independent activation of estrogen receptor by cyclin D1. Cell. 1997 Feb 7;88(3):405–415. [PubMed]

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