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Horm Metab Res 2006; 38(4): 236-240
DOI: 10.1055/s-2006-925337
Review
© Georg Thieme Verlag KG Stuttgart · New York

Sex Hormone-binding Globulin (SHBG) and Estradiol Cross-talk in Breast Cancer Cells

N.  Fortunati1 , M.  G.  Catalano2
  • 1 Oncological Endocrinology, ASO San Giovanni Battista, Turin, Italy
  • 2 Department of Clinical Physiopathology, University of Turin, Turin, Italy
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Publikationsverlauf

Received 1 August 2005

Accepted after revision 21 November 2005

Publikationsdatum:
15. Mai 2006 (online)

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Abstract

Sex Hormone-binding Globulin (SHBG) is a plasma glycoprotein that regulates the action of steroid hormones at several levels. SHBG regulates the availability of free androgens and estradiol to hormone-responsive tissues. Moreover, SHBG is also part of a novel steroid signaling system. We report here on the mechanism of action and the biological effects of SHBG in breast cancer cells, especially distinguishing cross-talk between membrane-initiated SHBG and estradiol pathways. After interacting with a specific binding site on breast cancer cell membranes, SHBG activates a specific pathway, and by cAMP induction, inhibits estradiol-mediated activation of ERK. Both estradiol and SHBG membrane-initiated pathways involve cross-talk at MAP kinase level with the ultimate result of inhibiting estradiol-mediated cell growth and antiapoptosis. On the basis of reported evidence, we suggest that SHBG is one of the regulators of growth and apoptosis of estrogen-dependent breast cancer cells.

Key words

SHBG · breast cancer · estradiol effect · SHBG membrane binding site

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