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DOI: 10.1055/s-2006-925337
Sex Hormone-binding Globulin (SHBG) and Estradiol Cross-talk in Breast Cancer Cells
Publication History
Received 1 August 2005
Accepted after revision 21 November 2005
Publication Date:
15 May 2006 (online)
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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Nicoletta Fortunati, M. D.
Lab. Endocrinologia Oncologica
Via Genova 3 · 10126 Torino · Italy ·
Fax: +39-011-670.5366
Email: nfortunati@molinette.piemonte.it