Sex steroid-binding protein and its membrane receptor in estrogen-dependent breast cancer: biological and pathophysiological impact.
Data obtained in our laboratory about the membrane receptor for sex steroid-binding protein (SBP-R) in human breast cancer are reported. SBP-R was detected in MCF-7 cells (estrogen receptor positive, ER+), while MDA-MB 231 cells (ER-) did not bind SBP. MCF-7 cells treated with SBP and E2 showed a marked increase of intracellular cAMP, and a significant reduction of both E2 induced cell proliferation and E2-mediated increase of progesterone receptor (PGR). The inhibition of E2 effects in MCF-7 cells was shown to be highly specific for SBP and mediated by protein kinase A, the target of cAMP. Membrane SBP-R was also evaluated in primary breast cancers. SBP-R was detectable only on ER+/PR+ samples and SBP-R+ samples presented a lower proliferation rate than negative samples. Our data, thus suggest that SBP-R and ER could be functionally related and also that SBP could modulate estrogen action at target cell site.
Fortunati
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II Division Universitaria di Medicina Generale, University of Torino Medical School, Italy.
Fissore
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Comba
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Becchis
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Catalano
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Fazzari
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Berta
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Frairia
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D001943:Breast Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004967:Estrogens; D011956:Receptors, Cell Surface; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases