Nott Stephanie L, Huang Yanfang, Fluharty Brian R, Sokolov Anna M, Huang Melinda, Cox Cathleen, Muyan Mesut
Department of Biochemistry & Biophysics, University of Rochester Medical School, Rochester, NY, 14642, USA.
Curr Pharmacogenomics Person Med. 2008 Dec 1;6(4):239-259. doi: 10.2174/187569208786733820.
Estrogen hormones play critical roles in the regulation of many tissue functions. The effects of estrogens are primarily mediated by the estrogen receptors (ER) alpha and beta. ERs are ligand-activated transcription factors that regulate a complex array of genomic events that orchestrate cellular growth, differentiation and death. Although many factors contribute to their etiology, estrogens are thought to be the primary agents for the development and/or progression of target tissue malignancies. Many of the current modalities for the treatment of estrogen target tissue malignancies are based on agents with diverse pharmacology that alter or prevent ER functions by acting as estrogen competitors. Although these compounds have been successfully used in clinical settings, the efficacy of treatment shows variability. An increasing body of evidence implicates ERalpha polymorphisms as one of the contributory factors for differential responses to estrogen competitors. This review aims to highlight the recent findings on polymorphisms of the lately identified ERbeta in order to provide a functional perspective with potential pharmacogenomic implications.
雌激素在许多组织功能的调节中起着关键作用。雌激素的作用主要由雌激素受体（ER）α和β介导。ER是配体激活的转录因子，可调节一系列复杂的基因组事件，这些事件协调细胞的生长、分化和死亡。尽管许多因素导致其发病，但雌激素被认为是靶组织恶性肿瘤发生和/或进展的主要因素。目前许多治疗雌激素靶组织恶性肿瘤的方法是基于具有不同药理学特性的药物，这些药物通过作为雌激素竞争者来改变或阻止ER功能。尽管这些化合物已在临床中成功使用，但治疗效果存在差异。越来越多的证据表明，ERα多态性是对雌激素竞争者产生不同反应的促成因素之一。本综述旨在强调最近在新发现的ERβ多态性方面的研究结果，以便从功能角度提供具有潜在药物基因组学意义的观点。
