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1篇 您的检索式:作者名="Donald Poirier"
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1Synergistic control of sex hormones by 17β-HSD type 7: a novel target for estrogen-dependent breast cancer显示文摘17β-hydroxysteroid dehydrogenase(17β-HSD)type 1 is known as a critical target to block the final step of estrogen production in estrogen-dependent breast cancer.Recent confirmation of the role of dyhydroxytestosterone(DHT)in counteracting estrogeninduced cell growth prompted us to study the reductive 17β-HSD type 7(17β-HSD7),which activates estrone while markedly inactivatingDHT.The role ofDHTin breast cancer cell proliferation isdemonstratedby its independent suppression of cell growthin the presence of a physiological concentration of estradiol(E2).Moreover,an integral analysis of a large number of clinical samples in Oncomine datasets demonstrated the overexpression of 17β-HSD7 in breast carcinoma.Inhibition of 17β-HSD7 in breast cancer cells resulted in a lower level of E2 and a higher level of DHT,successively induced regulation of cyclinD1,p21,Bcl-2,and Bik,consequently arrested cell cycle in the G0/G1 phase,and triggered apoptosis and auto-downregulation feedback of the enzyme.Such inhibition led to significant shrinkage of xenograft tumors with decreased cancer cell density and reduced 17β-HSD7 expression.Decreased plasma E2 and elevated plasma DHT levels were also found.Thus,the dual functional 17β-HSD7 is proposed as a novel target for estrogen-dependent breast cancer by regulating the balance of E2 andDHT.Thisdemonstrates aconceptual advance on the general belief that the major role of this enzyme is in cholesterol metabolism.Xiaoqiang Wang Catherine Gérard Jean-Francois Thériault Donald Poirier Charles J.Doillon Sheng-Xiang Lin 2015Journal of Molecular Cell Biology2015,7,6:2
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