Epigenetic Reactivation of Estrogen Receptor: Promising Tools for Restoring Response to Endocrine Therapy.
Epigenetic Reactivation of Estrogen Receptor: Promising Tools for Restoring Response to Endocrine Therapy.
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DOI：
10.4255/mcpharmacol.10.25
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发表时间：
2010-12
期刊：
影响因子：
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通讯作者：
N. Saxena;D. Sharma
中科院分区：
文献类型：
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作者：
N. Saxena;D. Sharma
表达雌激素受体α (ER)的乳腺肿瘤对使用选择性雌激素受体调节剂（SERMs）如他莫昔芬的治疗策略反应良好。然而，大约30%的浸润性乳腺癌是激素不依赖型的，因为它们由于ER启动子的高甲基化而缺乏ER表达。用去甲基化剂和组蛋白去乙酰化酶抑制剂治疗ER阴性乳腺癌细胞可导致ER mRNA和功能蛋白的表达。此外，生长因子信号通路也与ER阴性肿瘤表型中的ER沉默有关。近年来，泛素-蛋白酶体通路组分在介导内质网下调中发挥了重要作用。在本文中，我们将回顾ER阴性肿瘤表型中ER沉默的各种机制，并讨论对抗它的各种策略。正在进行的研究可能为设计针对雌激素受体阴性乳腺癌预防或治疗的表观遗传和非表观遗传机制的治疗策略提供机制见解。
Breast tumors expressing estrogen receptor alpha (ER) respond well to therapeutic strategies using SERMs (selective estrogen receptor modulators) such as tamoxifen. However, about thirty percent of invasive breast cancers are hormone independent because they lack ER expression due to hypermethylation of ER promoter. Treatment of ER-negative breast cancer cells with demethylating agents and histone deacetylase inhibitors leads to expression of ER mRNA and functional protein. Additionally, growth factor signaling pathways have also been implicated in ER silencing in ER-negative tumor phenotype. Recently, important role of components of ubiquitin-proteasome pathway has been shown in mediating downregulation of ER. In this article, we will review various mechanisms underlying the silencing of ER in ER negative tumor phenotype and discuss diverse strategies to combat it. Ongoing studies may provide the mechanistic insight to design therapeutic strategies directed towards epigenetic and non-epigenetic mechanisms in the prevention or treatment of ER-negative breast cancer.