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:

Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells

Oncogene volume 20, pages 5420–5430 (2001)Cite this article

Abstract

Membrane-associated binding sites for estrogen may mediate rapid effects of estradiol-17β that contribute to proliferation of human breast cancers. After controlled homogenization and fractionation of MCF-7 breast cancer cells, the bulk of specific estradiol binding is found in nuclear fractions. However, a significant portion of specific, high-affinity estradiol-17β binding-sites are also enriched in plasma membranes. These estradiol binding-sites co-purify with 5′-nucleotidase, a plasma membrane-marker enzyme, and are free from major contamination by cytosol or nuclei. Electrophoresis of membrane fractions allowed detection of a primary 67-kDa protein and a secondary 46-kDa protein recognized by estradiol-17β and by a monoclonal antibody directed to the ligand-binding domain of the nuclear form of estrogen receptor. Estrogen-induced growth of MCF-7 breast cancer cells in vitro was blocked by treatment with the antibody to estrogen receptor and correlated closely with acute hormonal activation of mitogen-activated protein kinase and Akt kinase signaling. Estrogen-promoted growth of human breast cancer xenografts in nude mice was also significantly reduced by treatment in vivo with the estrogen receptor antibody. Thus, membrane-associated forms of estrogen receptor may play a role in promoting intracellular signaling for hormone-mediated proliferation and survival of breast cancers and offer a new target for antitumor therapy.

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
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Ahmad S, Singh N, Glazer RI . 1999 Biochem. Pharmacol. 58: 425–430

  • An J, Tzagarakis-Foster C, Scharschmidt TC, Lomri N, Leitman DC . 2001 J. Biol. Chem. 276: 17808–17814

  • Aronica S, Katzenellenbogen B . 1993 Mol. Endocrinol. 7: 743–752

  • Aronica S, Kraus W, Katzenellenbogen B . 1994 Proc. Natl. Acad. Sci. USA 91: 8517–8521

  • Bergeron JJ, Searle N, Khan MN, Posner BI . 1986 Biochemistry 25: 1756–1764

  • Berthois Y, Pourreau-Schneider N, Gandilhon P, Mittre H, Tubiana N, Martin PM . 1986 J. Steroid Biochem. 25: 963–972

  • Chambliss K, Yuhanna I, Mineo C, Liu P, German Z, Sherman T, Mendelsohn M, Anderson R, Shaul P . 2000 Circ. Res. 87: e44–e52

  • Chen F, Watson CS, Gametchu B . 1999 J. Cell. Biochem. 74: 430–446

  • Chun TY, Gregg D, Sarkar DK, Gorski J . 1998 Proc. Natl. Acad. Sci. USA 95: 2325–2330

  • Couse JF, Curtis SW, Washburn TF, Lindzey J, Golding TS, Lubahn DB, Smithies O, Korach KS . 1995 Mol. Endocrinol. 9: 1441–1454

  • Evans RM . 1988 Science 240: 889–895

  • Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, Feeser WS, Van Dyk DE, Pitts WJ, Earl RA, Hobbs F, Copeland RA, Magolda RL, Scherle PA, Trzaskos JM . 1998 J. Biol. Chem. 273: 18623–18632

  • Flouriot G, Brand H, Denger S, Metivier R, Kos M, Reid G, Sonntag-Buck V, Gannon F . 2000 EMBO J. 19: 4688–4700

  • Fuqua SA, Schiff R, Parra I, Friedrichs WE, Su J-L, McKee DD, Slentz-Kesler K, Moore LB, Willson TM, Moore JT . 1999 Cancer Res. 59: 5425–5428

  • Germain PS, Metezeau P, Tiefenauer LX, Kiefer H, Ratinaud MH, Habrioux G . 1993 Anticancer Res. 13: 2347–2353

  • Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P . 1986 Nature 320: 134–139

  • Gu Q, Korach KS, Moss RL . 1999 Endocrinol. 140: 660–666

  • Hawkins MB, Thornton JW, Crews D, Skipper J, Dotte A, Thomas P . 2000 Proc. Natl. Acad. Sci. USA 97: 10751–10756

  • Haynes MP, Sinha D, Russell KS, Collinge M, Fulton D, Morales-Ruiz M, Sessa WC, Bender JR . 2000 Circ. Res. 87: 677–682

  • Henderson BE, Ross R, Bernstein L . 1988 Cancer Res. 48: 246–253

  • Improta-Brears T, Whorton AR, Codazzi F, York JD, Meyer T, McDonnell DP . 1999 Proc. Natl. Acad. Sci. USA 96: 4686–4691

  • Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Daniel Metzger, Pierre Chambon . 1995 Science 270: 1491–1494

  • Kim H, Lee J, Jeong J, Bae S, Lee H, Jo I . 1999 Biochem. Biophys. Res. Commun. 263: 257–262

  • Levin ER . 1999 Trends Endocrinol. Metab. 10: 374–377

  • Luconi M, Muratori M, Forti G, Baldi E . 1999 J. Clin. Endocrinol. Metab. 84: 1670–1678

  • McKenna NJ, O'Malley BW . 2000 Nat. Med. 6: 960–962

  • Mendelsohn ME, Karas RH . 1999 New Engl. J. Med. 340: 1801–1811

  • Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E, Auricchio F . 1996 EMBO J. 15: 1292–1300

  • Monje P, Boland R . 1999 Mol. Cell. Endocrinol. 147: 75–84

  • Murdoch FE, Gorski J . 1991 Mol. Cell. Endocrinol. 78: C103–C108

  • Nemere I, Farach-Carson MC . 1998 Biochem. Biophys. Res. Commun. 248: 443–449

  • Nenci I, Marchetti E, Marzola A, Fabris G . 1981 J. Steroid Biochem. 14: 1139–1146

  • Norfleet AM, Clarke CH, Gametchu B, Watson CS . 2000 FASEB J. 14: 157–165

  • Pappas TC, Gametchu B, Watson CS . 1995 FASEB J. 9: 404–410

  • Pietras RJ, Szego CM . 1975 Nature 253: 357–359

  • Pietras RJ, Szego CM . 1977 Nature 265: 69–72

  • Pietras RJ, Szego CM . 1979 J. Steroid Biochem. 11: 1471–1483

  • Pietras RJ, Szego CM . 1980 Biochem. J. 191: 743–760

  • Pietras RJ, Szego CM . 1984 Biochem. Biophys. Res. Commun. 123: 84–91

  • Pietras RJ, Fendly BM, Chazin VR, Pegram M, Howell SB, Slamon DJ . 1994 Oncogene 9: 1829–1838

  • Pietras RJ, Arboleda J, Reese D, Wongvipat N, Pegram M, Ramos L, Gorman C, Parker MG, Sliwkowski M, Slamon DJ . 1995 Oncogene 10: 2435–2446

  • Ramirez VD, Zheng J . 1996 Front Neuroendocrinol. 17: 402–439

  • Razandi M, Pedram A, Greene GL, Levin ER . 1999 Mol. Endocrinol. 13: 307–319

  • Razandi M, Pedram A, Levin ER . 2000 Mol. Endocrinol. 14: 1434–1447

  • Register TC, Adams MR . 1998 J. Steroid Biochem. Mol. Biol. 64: 187–191

  • Russell KS, Haynes MP, Sinha D, Clerisme E, Bender JR . 2000 Proc. Natl. Acad. Sci. USA 97: 5930–5935

  • Sica V, Nola E, Parikh I, Puca GA, Cuatrecasas P . 1973 Nat. New Biol. 244: 36–39

  • Simoncini T, Hafezi-Moghadam A, Brazil D, Ley K, Chin W, Liao JK . 2000 Nature 407: 538–541

  • Stevis PE, Deecher DC, Suhadolnik L, Mallis LM, Frail DE . 1999 Endocrinology 140: 5455–5458

  • Szego CM, Davis JS . 1967 Proc. Natl. Acad. Sci. USA 58: 1711–1718

  • Szego CM, Pietras RJ . 1984 Int. Rev. Cytol. 88: 1–302

  • Watson CS, Gametchu B . 1999 Proc. Soc. Exp. Biol. Med. 220: 9–19

  • Watters JJ, Campbell JS, Cunningham MJ, Krebs EG, Dorsa DM . 1997 Endocrinology 138: 4030–4033

  • Weiler PJ, Wiebe JP . 2000 Biochem. Biophys. Res. Commun. 272: 731–737

  • Weisz A, Bresciani F . 1993 Crit. Rev. Oncol. 4: 361–388

  • Welshons WV, Grady LH, Judy BM, Jordan VC, Preziosi DE . 1993 Mol. Cell. Endocrinol. 94: 183–194

  • Zyzek E, Dufy-Barbe L, Dufy B, Vincent JD . 1981 Biochem. Biophys. Res. Commun. 102: 1151–1157

Download references

Acknowledgements

We acknowledge Dr E Montecino and C-P Ng for assistance with flow cytometry. Dr M Parker generously provided ERE-CAT reporter gene constructs, and Dr H Garban and Dr CM Szego offered helpful discussions and comments. Support from US Army DAMD17-001-0177.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, CA 90095-1678, California, USA

    Diana C Márquez & Richard J Pietras

Authors
  1. Diana C Márquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard J Pietras
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard J Pietras.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Márquez, D., Pietras, R. Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells. Oncogene 20, 5420–5430 (2001). https://doi.org/10.1038/sj.onc.1204729

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204729

Keywords

This article is cited by

Search

Advanced search

Quick links