孕激素受体通过一种新的转录效应诱导 ErbB-2 核转位，促进乳腺癌生长：ErbB-2 作为 Stat3 共激活因子发挥作用。
Progesterone receptor induces ErbB-2 nuclear translocation to promote breast cancer growth via a novel transcriptional effect: ErbB-2 function as a coactivator of Stat3.
机构信息
Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires C1428ADN, Argentina.
出版信息
Mol Cell Biol. 2010 Dec;30(23):5456-72. doi: 10.1128/MCB.00012-10. Epub 2010 Sep 27.
Abstract
Progesterone receptor (PR) and ErbB-2 bidirectional cross talk participates in breast cancer development. Here, we identified a new mechanism of the PR and ErbB-2 interaction involving the PR induction of ErbB-2 nuclear translocation and the assembly of a transcriptional complex in which ErbB-2 acts as a coactivator of Stat3. We also highlighted that the function of ErbB-2 as a Stat3 coactivator drives progestin-induced cyclin D1 promoter activation. Notably, PR is also recruited together with Stat3 and ErbB-2 to the cyclin D1 promoter, unraveling a new and unexpected nonclassical PR genomic mechanism. The assembly of the nuclear Stat3/ErbB-2 transcriptional complex plays a key role in the proliferation of breast tumors with functional PR and ErbB-2. Our findings reveal a novel therapeutic intervention for PR- and ErbB-2-positive breast tumors via the specific blockage of ErbB-2 nuclear translocation.
摘要
孕激素受体（PR）和 ErbB-2 双向交流参与乳腺癌的发生。在这里，我们发现了 PR 和 ErbB-2 相互作用的一个新机制，涉及 PR 诱导 ErbB-2 核转位以及形成转录复合物，其中 ErbB-2 作为 Stat3 的共激活因子。我们还强调，ErbB-2 作为 Stat3 共激活因子的功能驱动孕激素诱导的细胞周期蛋白 D1 启动子激活。值得注意的是，PR 也与 Stat3 和 ErbB-2 一起被招募到细胞周期蛋白 D1 启动子上，揭示了一种新的、出乎意料的非经典 PR 基因组机制。核 Stat3/ErbB-2 转录复合物的组装在具有功能性 PR 和 ErbB-2 的乳腺癌增殖中起着关键作用。我们的研究结果揭示了一种通过特异性阻断 ErbB-2 核转位治疗 PR 和 ErbB-2 阳性乳腺癌的新方法。
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