乳腺癌中雌激素受体α表达水平调节的分子机制
收稿日期: 2009-11-24
修回日期: 2010-02-04
网络出版日期: 2010-03-15
基金资助
国家自然科学基金项目(编号：30530320, 30625035)资助
Molecular mechanisms of regulation of estrogen receptor a expression level in breast cancer
Received date: 2009-11-24
Revised date: 2010-02-04
Online published: 2010-03-15
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ERa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ERα mRNA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。
程龙，黄翠芬，叶棋浓 . 乳腺癌中雌激素受体α表达水平调节的分子机制[J]. 遗传, 2010 , 32(3) : 191 -197 . DOI: 10.3724/SP.J.1005.2010.00191
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 induction 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 ERa expression at different levels.
Key words： breast cancer; gene expression regulation; estrogen receptor α
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