Cooperative interaction between retinoic acid receptor-α and estrogen receptor in breast cancer
Cooperative interaction between retinoic acid receptor-α and estrogen receptor in breast cancer
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DOI：
10.1101/gad.552910
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发表时间：
2010-01-15
影响因子：
10.5
通讯作者：
Carroll, Jason S.
中科院分区：
文献类型：
--
作者：
Ross-Innes, Caryn S.;Stark, Rory;Carroll, Jason S.
维甲酸受体α(RARα)是乳腺癌细胞中已知的雌激素靶基因。雌激素诱导RARα的结果以前是未知的。我们现在证明，RARα是雌激素受体α(ER)介导的有效转录和细胞增殖所必需的。RARα可以与ER结合位点相互作用，但这是以ER依赖的方式发生的，这为RARα提供了一个独立于其经典角色的新角色。我们在全基因组范围内证明，RARα和ER可以共同占据染色质内的调节区。当接触到主要的乳腺癌激素雌激素时，这种转录上活跃的共居和依赖发生--这种相互作用是由RARα的雌激素-ER诱导促进的。这些发现表明，RARα是ER复合体的重要组成部分，可能通过维持ER-辅因子的相互作用，并表明不同的核受体可以协同作用，在乳腺癌细胞中进行有效的转录活动。
Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen-an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells.