PRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-α in breast cancer
PRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-α in breast cancer
复制标题
DOI：
10.1038/sj.onc.1206578
复制
发表时间：
2003-06-05
期刊：
影响因子：
8
通讯作者：
Giordano, A
中科院分区：
文献类型：
--
作者：
Macaluso, M;Cinti, C;Giordano, A
雌激素受体-α (ER) 在正常乳房发育中起着至关重要的作用，也与乳腺癌的发生和进展有关。乳腺癌中 ER-α 基因的转录抑制是一个正在积极研究的领域，具有潜在的临床意义。然而，调节 ER-α 基因表达的分子机制尚不完全清楚。在这里，我们展示了 ER 阴性乳腺癌细胞中 pRb2/p130 介导的 ER-alpha 基因失活的新分子机制。我们研究了 pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 和 pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 复合物对 ER-α 启动子的体内占据情况，并提供了 pRb2/p130 和染色质修饰酶在生理环境下 ER-α 转录调节中的联系。这些发现表明，pRb2/p130-多分子复合物可能是调节 ER-α 基因表达的关键元件，并且可能被视为开发治疗乳腺癌的新型治疗策略的有希望的靶标，特别是对于 ER 阴性的肿瘤。
The estrogen receptor-alpha (ER) plays a crucial role in normal breast development and is also linked to development and progression of mammary carcinoma. The transcriptional repression of ER-alpha gene in breast cancer is an area of active investigation with potential clinical significance. However, the molecular mechanisms that regulate the ER-alpha gene expression are not fully understood. Here we show a new molecular mechanism of ER-alpha gene inactivation mediated by pRb2/p130 in ER-negative breast cancer cells. We investigated in vivo occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between pRb2/p130 and chromatin-modifying enzymes in the regulation of ER-alpha transcription in a physiological setting. These findings suggest that pRb2/p130-multimolecular complexes can be key elements in the regulation of ER-alpha gene expression and may be viewed as promising targets for the development of novel therapeutic strategies in the treatment of breast cancer, especially for those tumors that are ER negative.