Estrogen Modulation of Human Breast Cancer Cell Growth

  • Published : 1997.12.01

Abstract

To gain further insight into how estrogens modulate cell function, the effects of estrogen on cell proliferation were studied inhuman breast cancer cells. We examined the effects of estrogen on the proliferation of three human breast cancer cell lines that differed in their estrogen receptor contents. Ten nM estradiol markedly stimulated the proliferation of MCF-7 human breast cancer cells that contained high levels of estrogen receptor $1.15{\pm}0.03 pmole/mg protein)$(over that of control. In T47D cells that contained low levels of estrogen receptor $0.23{\pm}0.05 pmole/mg protein)$, Ten nM estrogen slightly stimulated the proliferation over that of control. MDA-MB-231 cells, that contained no detectable levels of estrogen receptors, had their growth unaffected by estrogen. These results showed their sensitivity to growth stimulation by estrogen correlated well with their estrogen receptor content. Also we examined the effect of estrogen on cellular progesterone receptor level as well as plasminogen activator activity in MCF-7 cells. Ten nM estradiol showed maximal stimulation of progesterone receptor level as well as plasminogen activator activity in MCF-7 cells. It is not clear whether these stimulations of progesterone receptor and plasminogen activator activity by estrogen are related to the estrogen stimulation of cell proliferation of MCF-7 cells. Studies with estrogen in human breast cancer cells in culture indicate that sensitivity to growth stimulation by estrogen correlates well with estrogen receptor contents.

References

  1. J. Cell. Biochem. Suppl. v.17G c-erbB-2 amplifcation in mammary carcinoma Barnes,D.M.
  2. Cancer Res. v.127 What did we learn from the results of the international overview about the effects of endocrine therapy? Recent Results Bonadonna,G.
  3. Cancer Res. v.43 steroid stimulation of plasminogen activator production in a human breast cancer cell line (MCF-7) Butler,W.B.;Kirkland,W.L.;Gayala,T.L.;Goran,N.;Kelesey,W.H.;Berkinski,P.J.
  4. Cancer Res. v.46 Use of two MCF-7 cell variants to evaluate the growth regulatory potential of estrogen-induced products Davidson,N.E.;Bronzert,D.A.;Chambon,P.;Gelmann,E.P.;Lippman,M.E.
  5. Adv. Exp. Med. Biol. v.330 Breast Cancer: Influence of endocrine hormones, growth factors, and genetic alterations Dickson,R.B.;Johnson,M.D.;Ashry D. EL;Shi,Y.E.;Bano,M.;Zugmaier,G.;Ziff,B.;Lippman,M.E.
  6. Mol. Biol. v.37 Regulation of proliferation, invasion, and growth factor synthesis in breast cancer by steroids Dickson,R.B.;Thompson,E.W.;Lipmann,M.E.
  7. Cancer Res. v.42 Effects of estrogens and antiestrogens on estrogen receptor dynamics and the induction of progesterone receptor in MCF-7 human breast cancer cells Eckert,R.L.;Katzellenbogen,B.S.
  8. Breast Cancer Res. Treat. v.1 Estradiol stimulates synthesis of a major intracellular protein in the human breast cancer cell line MCF-7 Edward,D.P.;Adams,D.J.;McGuire,W.L.
  9. Recent Result Cancer Res. v.127 Adjuvant systemictherapy; overview Henderson,I.C.
  10. Breast Cancer Res. and Treatment. v.5 Antiestrogen action in breast cancer cells Katzellenbogen,B.S.;Miller,M.A.;Mullick,A.;Sheen,Y.Y.
  11. Nature v.307 Monoclonal antibodies localize estrogen receptor in nuclei of target cells King,W.J.;Green,G.L.
  12. Endocrine-dependent Tumros Regulation of growth inhibitory polypeptides in human breast cancer Knabbe,C.;Voigt,K.D.(ed.);Knabee,C.(ed.)
  13. Endocrinology v.111 Uterine plasminogen activator: modulation by steroid hormones Kneifel,M.A.;Leytus,S.P.;Fletcher,E.;Weger,T.;Mangel,W.F.;Katzellenbogen,B.S.
  14. Biochem. Biophys. Acta v.788 Theory and experimental method for determining kinetic constants of fast-acting irreversible protease inhibitors Leytus,S.P.;Toledo,D.L.;Mangel,W.F.
  15. Adv. Intern. Med. v.24 Steroid receptor sites in cancer therapy McGuire,W.L.
  16. Adv. Cancer Res. v.17 Mammary neoplasia in mice Nandi,S.;McGrath,C.M.
  17. Hum. Pathol. v.24 p53 protein expression in mammary ductal carcinoma in situ Poller,D.N.;Roberts,E.C.;Bell,J.A.;Elston,C.W.;Blamy,R.W.;Ellis,I.O.
  18. Ann. NY Acad. Sci. v.51 The attractions of protein for small molecule and ions Schatchard,G.
  19. Adv. Cancer Res. v.61 Molecular genetic changes in human breast cancer van de Vijver, M. J.
  20. Cancer Res. v.43 Release of estrogen-induced glycoprotein with a molecular weight of 52,000 by breast cancer cells in primary culture Veith,F.O.;Capony,F.;Garcia,M.;Chantelard,J.;Pujol,H.;Veith,F.;Zajdela;Rochefort,H.
  21. Nature v.307 Nuclear localization of unoccupied estrogen receptors Welshons,W.V.;Liebeman,M.E.;Gorski,J.
  22. J. Biol. Chem. v.259 Effect of antiestrogen on the estrogen regulated p53 RNA and the 52- and 160-kilodalton proteins in MCF-7 cells and two tamoxifen-resistant sublines Westley,B.;May,F.E.B.;Brown,M.C.;Krust,A.;Chambon,P.;Rochefort,H.
  23. Cell v.20 A secreted glycoprotein induced by estrogen in human breast cancer cell lines Westley,B.;Rochefort,H.
  24. Ann. Rev. Genet. v.19 Steroid receptor regulated transcription of specific genes and gene networks Yamamoto,K.R.