【摘 要】
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XAP2 has recently been identified as tumor suppressor through studies of familial mutations in the XAP2 gene that lead to pituitary tumors and other organs such as the female reproductive tract.Howeve
【机 构】
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Department of Biosciences and Nutrition Karolinska Institutet Sweden
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XAP2 has recently been identified as tumor suppressor through studies of familial mutations in the XAP2 gene that lead to pituitary tumors and other organs such as the female reproductive tract.However, the molecular mechanisms behind the tumor suppressive effects of XAP2 are currently unknown.In this study, we show that XAP2 could be recruited to the promoter of breast cancer marker gene pS2 and negatively regulate pS2 expression in MCF-7 cells.Interestingly, XAP2 could prevent E2-dependent transcriptional activity in an estrogen receptor (ER) isoform-specific manner: XAP2 inhibits ER but not ER-mediated transcription.Thus, disruption of XAP2 activity leads to increased ER activity and possibly promotes the tumorigenic effects of estrogen.In addition, our results indicate that inhibitory effect of XAP2 is mediated by the AF-1 domain of ER through AF-1 associated factors, such as the classical p160 co-activator TIF-2.Taking together, this study shows that XAP2 exerts a negative effect on ER transcriptional activity through negative regulation of TIF-2 and may thus prevent ER-dependent tumor growth.
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