Targeting the genotoxic effects of estrogens

Monica M. Montano, Nirmala Krishnamurthy, Smitha Sripathy
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Abstract

Our studies indicate that expression of antioxidative stress enzymes is upregulated by Selective Estrogen Receptor Modulators (SERMs) in breast epithelial cell lines, providing protection against the genotoxic effects of estrogens and against estrogen-induced mammary tumorigenesis. This upregulation of antioxidative stress enzymes requires Estrogen Receptor beta (ERβ) and human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2). Further studies indicate that hPMC2 has a functional exonuclease domain that is required for upregulation of antioxidative stress enzymes by SERMs and repair of estrogen-induced abasic sites.

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针对雌激素的基因毒性效应
我们的研究表明,选择性雌激素受体调节剂(SERMs)可以上调乳腺上皮细胞系中抗氧化应激酶的表达,从而保护乳腺细胞免受雌激素的遗传毒性作用和雌激素诱导的乳腺肿瘤发生。这种抗氧化应激酶的上调需要雌激素受体β (ERβ)和人爪蟾有丝分裂突变基因同源物(hPMC2)。进一步的研究表明,hPMC2具有一个功能性外切酶结构域,该结构域是SERMs上调抗氧化应激酶和修复雌激素诱导的基础位点所必需的。
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