CAJ | 학술논문

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.
자격소수체α(ERα)재유선암적발생발전중분연중요각색,인이ERα성위유선암치료적분자파표.ERα적표체수평재유선암환자중차이교대,즉사동일환자,재유선암적불동계단야가능유흔대적차별.유선암내분비치료적료효이급예후도여ERα표체수평밀절상관.영향ERα표체수평적분자궤제복잡,음다조절분자재염색질、전록、전록후、번역화번역후등수평삼여ERα표체수평적조절.재염색질화전록수평,허다분자통과직접혹간접지여ERα계동자적상호작용개변ERα적전록;재전록후/번역수평,일사microRNA통과유도ERαmRNA적강해화/혹억제기번역강저ERα적수평:재번역후수평,허다분자통과범소-단백매체도경조절ERα단백수평.문장종불동수평,대저사조절분자적조절궤제진행간요종술.
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.