Epigenetics of estrogen receptor signaling: role in hormonal cancer progression and therapy.
Epigenetics of estrogen receptor signaling: role in hormonal cancer progression and therapy.
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DOI：
10.3390/cancers3021691
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发表时间：
2011-03-29
期刊：
影响因子：
5.2
通讯作者：
Vadlamudi RK
中科院分区：
文献类型：
--
作者：
Mann M;Cortez V;Vadlamudi RK
雌激素受体（ERα）信号在激素性癌症的进展中起关键作用。ERα是一种依赖配体的转录因子，通过招募到靶基因染色质来调节基因转录。新出现的证据表明，ERα信号传导有可能促进表观遗传变化。雌激素刺激可通过与组蛋白修饰酶的动态相互作用诱导ERα靶基因启动子上的多种组蛋白修饰，包括乙酰化、磷酸化和甲基化。参与ERα介导的表观遗传途径的酶的解除可能在ERα驱动的肿瘤过程中发挥重要作用。与遗传改变不同，表观遗传改变是可逆的，因此为逆转ERα驱动的表观遗传改变提供了新的治疗机会。在这篇综述中，我们总结了目前关于ERα信号通过组蛋白修饰增强癌细胞表观遗传变化的机制的知识。
Estrogen receptor (ERα) signaling plays a key role in hormonal cancer progression. ERα is a ligand-dependent transcription factor that modulates gene transcription via recruitment to the target gene chromatin. Emerging evidence suggests that ERα signaling has the potential to contribute to epigenetic changes. Estrogen stimulation is shown to induce several histone modifications at the ERα target gene promoters including acetylation, phosphorylation and methylation via dynamic interactions with histone modifying enzymes. Deregulation of enzymes involved in the ERα -mediated epigenetic pathway could play a vital role in ERα driven neoplastic processes. Unlike genetic alterations, epigenetic changes are reversible, and hence offer novel therapeutic opportunities to reverse ERα driven epigenetic changes. In this review, we summarize current knowledge on mechanisms by which ERα signaling potentiates epigenetic changes in cancer cells via histone modifications.