Sex hormone-binding globulin (SHBG) and estradiol cross-talk in breast cancer cells.
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.
Fortunati
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Oncological Endocrinology, ASO San Giovanni Battista, Turin, Italy. nfortunati@molinette.piemonte.it
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D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D015398:Signal Transduction
D008565:Membrane Proteins; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol