针对雌激素的基因毒性作用
TARGETING THE GENOTOXIC EFFECTS OF ESTROGENS.
作者信息
Montano Monica M, Krishnamurthy Nirmala, Sripathy Smitha
机构信息
Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106.
出版信息
Drug Discov Today Dis Mech. 2012 Summer;9(1-2):e29-e33. doi: 10.1016/j.ddmec.2012.11.005.
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.
摘要
我们的研究表明，在乳腺上皮细胞系中，选择性雌激素受体调节剂（SERM）可上调抗氧化应激酶的表达，从而为抵御雌激素的基因毒性作用以及雌激素诱导的乳腺肿瘤发生提供保护。抗氧化应激酶的这种上调需要雌激素受体β（ERβ）和非洲爪蟾基因的人类同源物（该同源物可预防有丝分裂灾难，即hPMC2）。进一步的研究表明，hPMC2具有一个功能性核酸外切酶结构域，这是SERM上调抗氧化应激酶以及修复雌激素诱导的无碱基位点所必需的。
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