乳腺癌中雌激素受体α表达水平调节的分子机制
Molecular mechanisms of regulation of estrogen receptor α expression level in breast cancer
程龙 1黄翠芬 1叶棋浓1
作者信息
- 1. 军事医学科学院生物工程研究所,北京,100850
- 折叠
摘要
雌激素受体α(ERα)在乳腺癌的发生发展中扮演重要角色,因而ERα成为乳腺癌治疗的分子靶标.ERα的表达水平在乳腺癌患者中差异较大,即使同一患者,在乳腺癌的不同阶段也可能有很大的差别.乳腺癌内分泌治疗的疗效以及预后都与ERα表达水平密切相关.影响ERα表达水平的分子机制复杂,众多调节分子在染色质、转录、转录后、翻译和翻译后等水平参与ERα表达水平的调节.在染色质和转录水平,许多分子通过直接或间接地与ERα启动子的相互作用改变ERα的转录;在转录后/翻译水平,一些microRNA通过诱导ERαmRNA的降解和/或抑制其翻译降低ERα的水平:在翻译后水平,许多分子通过泛素-蛋白酶体途径调节ERα蛋白水平.文章从不同水平,对这些调节分子的调节机制进行简要综述.
Abstract
Estrogen receptor α(ERα) plays an important role in breast cancer development and progression and thus becomes a useful molecular target for breast cancer therapy.ERα is differentially expressed in breast cancer patients.Moreover,ERα expression levels may change at different stages of breast cancer even for the same patient.ERα expression is closely associated with the effect of endocrine therapy and prognosis.The mechanisms underlying ERα expression are complicated,because ERα expression is regulated at different levels,including chromatin,transcriptional,post-transcriptional,translational,and post-translational levels.Many proteins modulate the transcription of ERα gene at the chromatin and transcriptional levels through direct or indirect interaction with the ERα promoter.Some microRNAs decrease ERα levels possibly by induetiun of the degradation of ERα mRNA and/or repression of the mRNA translation.At the post-translational level,many proteins regulate ERα protein levels through ubiquitin-proteosome pathway.This review focuses on molecular mechanisms of regulation of ERα expression at different levels.
关键词
乳腺癌/基因表达调控/雌激素受体αKey words
breast cancer/gene expression regulation/estrogen receptor α引用本文复制引用
基金项目
国家自然科学基金(30530320)
国家自然科学基金(30625035)
出版年
2010
NETL
NSTL
维普
万方数据