The Roles of Xeno-oestrogens in Androgen Receptor mediated transactivation

来源 :第四届细胞结构与功能的信号基础研讨会 | 被引量 : 0次 | 上传用户:wjsxyxjc
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  Prostate cancer is the second leading cause of cancer death among males in the United States and significantly increases in Asian countries.Prostate cancer is sensitive to hormone regulation and associated with extemporaneous exposure to some endocrine disruptors (xeno-oestrogens).It is very important to set up a system to evaluate the effect of the exposure to a certain xeno-oestrogen and further to reveal its association with the risk of prostate cancer.In this study we cloned the three androgen response elements (AREs, includingAREⅠ, AREⅡ, and AREⅢ) with a core transactivation TATA element of the prostate-specific antigen (PSA) promoter into pGL2 basic vector to create an artificial pGL2/AREs-TATA reporter system, which was applied to evaluate the effects of different xeno-oestrogens (bisphenol A, 4-nonylphenol,dichlorodiphenyl trichloroethane [DDT] or diethylstilbestrol [DES]) on androgen receptor (AR) abnormal activation to regulate PSA expression and cell proliferation.In all three AREs, AREⅢ-TATA displayed as a major element responsive to AR-mediated DHT stimulation of the PSA promoter.Therefore, pGL2/AREⅢ-TATA reporter was adopted to analyze the AR activated possibilities by four different xeno-oestrogens.Bisphenol A or DES significantly induced AR-mediated transcriptional activity of AREⅢ-TATA reporter, whereas DDT or 4-nonylphenol did not.Moreover, AR-mediated cell proliferation in response to each of four xeno-oestrogens was measured in a MTT assay.Bisphenol A or DES, as an AR inducer, exhibited an enhanced effect in cell proliferation, rather than the effect of DDT or 4-nonylphenol.Taken together, four xeno-oestrogens were identified to have different activities on AR.Bisphenol A and DES can be regarded as androgenic effectors of regulation PSA expression and cell proliferation.
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