Growth inhibition by anti-estrogens and progestins in TGF-beta-resistant and -sensitive breast-tumor cells

International Journal of Cancer. Journal International Du Cancer
E KalkhovenB van der Burg

Abstract

Transforming growth factor beta (TGF-beta) is a potent growth inhibitor of non-malignant breast tissue, and TGF-beta resistance could play a role in tumorigenesis. Treatment of breast-tumor cells with anti-estrogens and progestins has been shown to correlate with an increase in the levels of secreted TGF-beta, suggesting that the growth inhibition observed with these (anti)hormones is mediated by this growth factor. In the present study we have investigated the effects of anti-estrogens and progestins on breast-tumor cell lines, which are either resistant or sensitive to TGF-beta. A hormone-independent variant of the MCF7 cell line is shown to have lost its sensitivity to TGF-beta during its progression towards an autonomous phenotype, but has preserved its sensitivity to anti-estrogens. In addition, evidence is presented showing that progestins and anti-estrogens inhibit proliferation, irrespective of the sensitivity to TGF-beta in variants of the T47D cell line. Therefore, we conclude that, although TGF-beta seems an important growth inhibitor for mammary epithelial cells, both progestins and anti-estrogens can inhibit cell proliferation independent of induced TGF-beta production.

References

May 1, 1990·Endocrine Reviews·C L Clarke, R L Sutherland
Jun 15, 1987·Clinica Chimica Acta; International Journal of Clinical Chemistry·M A BlankensteinJ H Thijssen
Oct 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·A M BrownP Chambon
Mar 29, 1995·International Journal of Cancer. Journal International Du Cancer·E KalkhovenB van der Burg
Jan 1, 1994·Breast Cancer Research and Treatment·C K Osborne, S A Fuqua
Jun 1, 1994·Molecular and Cellular Endocrinology·E KalkhovenB van der Burg

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Citations

Feb 13, 2009·The Journal of Biological Chemistry·Hany Abdel-HafizKathryn B Horwitz
May 6, 2009·Molecular and Cellular Biology·Deo Prakash Pandey, Didier Picard
Jan 8, 2010·Breast Cancer Research and Treatment·Selma MasriShiuan Chen
Mar 24, 2012·BMC Molecular Biology·Hany A Abdel-Hafiz, Kathryn B Horwitz
Feb 25, 2006·European Journal of Pharmacology·Daniela MalekBurkhard Kleuser
Dec 18, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Hany A Abdel-Hafiz, Kathryn B Horwitz
Jun 24, 1999·Molecular Endocrinology·T C SpelsbergS Khosla
Aug 12, 1998·The Journal of Steroid Biochemistry and Molecular Biology·E CastañoA C Notides
Aug 1, 1998·Toxicology in Vitro : an International Journal Published in Association with BIBRA·D DesaulniersW G Foster

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