Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest

Oncogene volume 21, pages 4626–4634 (2002)Cite this article

Abstract

Estrogens stimulate proliferation of estrogen receptor positive MCF7 breast cancer cells while antiestrogens signal a G0/G1 growth arrest. In MCF7 cells, arrest is mediated through the CDK inhibitors p21 and p27 and through a decrease in cyclin E/CDK2 kinase activity. We found that in MCF7 cells, overexpression of cyclin E partially abrogates a tamoxifen mediated growth arrest. Overexpression of cyclin E is accompanied by a decrease in the levels of RB and CDK inhibitor p21 but an increase in CDK inhibitor p27. Cyclin E overexpression also alters the composition of E2F transcription factor complexes. The E2F4/p107/cyclin E/CDK2 complex, a minor component in proliferating control cells that is absent in growth-arrested cells, is more abundant in both proliferating and tamoxifen treated cyclin E overexpressing cells. Conversely, levels of the quiescence associated E2F/p130 complex is not detected in these cells. Expression from the E2F dependant promoter is elevated in proliferating and tamoxifen treated cyclin E overexpressing cells. This study suggests that a modest overexpression of cyclin E abrogates the tamoxifen mediated growth arrest through modification of the RB/E2F pathway. Moreover, these results provide one explanation of why some cells that express the estrogen receptor may be unresponsive to antiestrogens.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Arata Y, Fujita M, Ohtani K, Kijima S, Kato JY . 2000 J. Biol. Chem. 275: 6337–6345

  • Beato M, Chavez S, Truss M . 1996 Steroids 61: 240–251

  • Bortner DM, Rosenberg MP . 1997 Mol. Cell. Biol. 17: 453–459

  • Buckley MF, Sweeney KJ, Hamilton JA, Sini RL, Manning DL, Nicholson RI, deFazio A, Watts CK, Musgrove EA, Sutherland RL . 1993 Oncogene 8: 2127–2133

  • Cariou S, Donovan CH, Flanagan WM, Milic A, Bhattacharya N, Slingerland JM . 2000 Proc. Natl. Acad. Sci. USA 97: 9042–9046

  • Carrol JS, Prall OWJ, Musgrove EA, Sutherland RL . 2000 J. Biol. Chem. 275: 38220–38221

  • Chiarle R, Pagano M, Inghirami G . 2001 Breast Canc. Res. 3: 91–94

  • Darzynkiewicz Z, Bedner E, Li X, Gorczyca W, Melamed MR . 1999 Cell. Res. 249: 1–12

  • Duronio RJ, Brook A, Dyson N, O'Farrell PH . 1996 Genes Dev. 10: 2505–2513

  • Dyson N . 1998 Genes Dev. 12: 2245–2262

  • Encarnacion CA, Ciocca DR, McGuire WL, Clark GM, Fuqua SA, Osborne CK . 1993 Breast Cancer Res. Tr. 26: 237–246

  • Harbour JW, Luo RX, Dei Santi A, Postigo AA, Dean DC . 1999 Cell 98: 859–869

  • Hartwell LH, Kastan MB . 1994 Science 266: 1821–1828

  • Hatakeyama M, Brill JA, Fink GR, Weinberg RA . 1994 Genes Dev. 8: 1759–1771

  • Hengst L, Dulic V, Slingher J, Lees E, Reed SI . 1994 Proc. Natl. Acad. Sci. USA 91: 5291–5294

  • Howell A, DeFriend D, Robertson JFR, Blamey RW, Anderson L, Anderson E, Sutcliffe FA, Walton P . 1996 Brit. J. Cancer 74: 300–308

  • Hunter T, Pines J . 1994 Cell 79: 573–582

  • Kamentsky LA . 2001 Methods Cell Biol. 63: 51–87

  • Katzenellenbogen JA, O'Malley BW, Katzenellenbogen BS . 1996 Mol. Endocrinol. 10: 119–131

  • Keyomarsi K, O'Leary N, Molnar C, Lees E, Fingert HJ, Pardee AB . 1994 Cancer Res. 54: 380–385

  • Keyomarsi K, Conte Jr D, Toyofuku W, Fox MP . 1995 Oncogene 11: 941–950

  • Koff A, Ohtsuki M, Polyak K, Roberts JM, Massague J . 1993 Science 260: 536–539

  • Lees E, Faha E, Duclic V, Reed SI, Harlow E . 1992 Genes Dev. 6: 1874–1885

  • Loeken MR, Brady J . 1989 J. Biol. Chem. 264: 6572–6579

  • Lundberg AS, Weinberg RA . 1998 Mol. Cell Biol. 18: 753–761

  • Maki CG, Howley PM . 1997 Mol. Cell. Biol. 17: 355–363

  • Mayol X, Grana X . 1997 Prog, Cell Cycle Res. 3: 157–169

  • Mudryj M, Devoto SH, Hiebert SW, Hunter T, Pines J, Nevins JR . 1991 Cell 65: 1243–1253

  • Nasmyth K . 1993 Curr. Opin. Cell Biol. 5: 166–179

  • Nevins JR . 1998 Cell Growth Differ 9: 585–593

  • Nielsen NH, Arnerlov C, Emdin SO, Landberg G . 1996 Brit. J. Cancer 74: 874–880

  • Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM, Pagano M . 1995 Mol. Cell. Biol. 15: 2612–2624

  • Perlmann T, Evans RM . 1997 Cell 90: 391–397

  • Porter DC, Keyomarsi K . 2000 Nucleic Acids Res. 28: E101

  • Robertson JFR . 1996 Brit. J. Cancer 73: 5–12

  • Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM . 1999 Mol. Cell Biol. 19: 4843–4854

  • Sambrook J, Fritsch EF, Maniatis T . 1989 Molecular Cloning: A Laboratory Manual 2nd ed Cold Spring Harbor Laboratory Press: New York pp 737–752

    Google Scholar 

  • Schulze A, Zerfass K, Spitkovsky D, Middendorp S, Berges J, Helin K, Jansen-Durr P, Henglein B . 1995 Proc. Natl. Acad. Sci. USA 92: 11264–11268

  • Sheaff RJ, Groudine M, Gordon M, Roberts JM, Clurman BE . 1997 Genes Dev. 11: 1464–1478

  • Sheaff RJ, Singer JD, Swanger J, Smitherman M, Roberts JM, Clurman BE . 2000 Mol. Cell. 5: 403–410

  • Sherr CJ . 1994 Cell 79: 551–555

  • Sherr CJ . 1996 Science 274: 1672–1677

  • Sherr CJ, Roberts JM . 1999 Genes Dev. 13: 1501–1512

  • Sgambato A, Han EK, Zhou P, Schieren I, Weinstein IB . 1996 Cancer Res. 56: 1389–1399

  • Su TT, O'Farrell PH . 1997 J. Cell Biol. 139: 13–21

  • Swanson C, Ross J, Jackson PK . 2000 Proc. Natl. Acad. Sci. USA 97: 7796–7801

  • Taylor IW, Hodson PJ, Green MD, Sutherland RL . 1983 Cancer Res. 43: 4007–4010

  • Vlach J, Hennecke S, Amati B . 1997 EMBO J. 16: 5334–5344

  • Watts CK, Brady A, Sarceciv B, de Fazio A, Musgrove EA, Sutherland RL . 1995 Mol. Endocrinol. 9: 1804–1813

  • Zerfass-Thome K, Schulze A, Zwerschke W, Vogt B, Helin K, Bartek J, Henglein B, Jansen-Durr P . 1997 Mol. Cell Biol. 17: 407–415

  • Zhao J, Dynlacht B, Imai T, Hori T, Harlow E . 1998 Genes Dev. 12: 456–461

Download references

Acknowledgements

We thank Daniel P Vang and Brian Robinson for technical support, and Drs Michael F Seldin, Gigi Lozano and Clifford Tepper for critical reading of the manuscript. This study was supported in part by a VA Merit Award (M Mudryj) and the University of California, Davis Health System Research Award (M Mudryj).

Author information

Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, 95616, California, CA, USA

    Navdeep K Dhillon

  2. Martinez VA, Martinez, 94553, California, CA, USA

    Maria Mudryj

Authors
  1. Navdeep K Dhillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Mudryj
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Mudryj.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dhillon, N., Mudryj, M. Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest. Oncogene 21, 4626–4634 (2002). https://doi.org/10.1038/sj.onc.1205576

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205576

Keywords

This article is cited by

Search

Advanced search

Quick links