Histone deacetylase inhibition and estrogen signalling in human breast cancer cells
Histone deacetylase inhibition and estrogen signalling in human breast cancer cells
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DOI：
10.1016/j.bcp.2004.04.031
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发表时间：
2004-09-15
影响因子：
5.8
通讯作者：
Cavaillès, V
中科院分区：
文献类型：
--
作者：
Margueron, R;Duong, V;Cavaillès, V
雌激素是一种类固醇激素，通过特定的核雌激素受体(ERα和ERβ)发挥作用，是乳腺癌生长的重要调节因素。这些受体通过招募具有不同酶活性的转录辅助因子来控制基因的表达，如针对组蛋白和非组蛋白底物的组蛋白乙酰转移酶或组蛋白去乙酰基酶(HDAC)。ERpha本身和一些转录调节因子已被证明是乙酰化的蛋白质。在过去的十年中进行的研究强调了HDACi作为转录活性的调节剂和一类新的治疗剂的作用。在人类癌细胞中，HDACs的抑制控制ERpha基因的表达和对部分抗雌激素如4-羟基他莫昔芬的转录活性的反应。各种HDACi强烈抑制乳腺癌细胞的增殖，ER阴性(ER-)似乎不如ER阳性(ER+)细胞系敏感。P21(WAF1/CIP1)基因的表达与ERA水平有关，可能在乳腺癌细胞对高乙酰化药物的这种差异反应中发挥作用。(C)2004 Elsevier Inc.保留所有权利。
Estrogens are steroid hormones, which act through specific nuclear estrogen receptors (ERalpha and ERbeta) and are important regulators of breast cancer growth. These receptors control gene expression by recruiting transcriptional cofactors that exhibit various enzymatic activities such as histone acetyltransferase or histone deacetylase (HDAC) which target histone as well as non-histone substrates. The ERalpha itself and some of the transcriptional regulators have been shown to be acetylated proteins. Research performed over the last decade has highlighted the role of HDAC inhibitors (HDACi) as modulators of transcriptional activity and as a new class of therapeutic agents. In human cancer cells, inhibition of HDACs controls the expression of the ERalpha gene and the transcriptional activity in response to partial antiestrogens such as 4-hydroxytamoxifen. Various HDACi strongly inhibit breast cancer cell proliferation and ERalpha-negative (ER-) appear less sensitive than ERalpha-positive (ER+) cell lines. p21(WAF1/CIP1) gene expression, in relation with ERa levels, could play a role in this differential response of breast cancer cells to hyperacetylating agents. (C) 2004 Elsevier Inc. All rights reserved.