Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression.
Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression.
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核表皮生长因子受体 (EGFR) 与信号转导子和转录激活子 5 (STAT5) 相互作用，激活 Aurora-A 基因表达。
DOI：
10.1093/nar/gkn417
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发表时间：
2008-08
影响因子：
14.9
通讯作者：
Chang, Wen-Chang
中科院分区：
文献类型：
--
作者：
Hung, Liang-Yi;Tseng, Joseph T.;Lee, Yi-Chao;Xia, Weiya;Wang, Ying-Nai;Wu, Min-Li;Chuang, Yu-Hsuan;Lai, Chein-Hsien;Chang, Wen-Chang
遗传物质维持的丧失是导致肿瘤发生的关键步骤。据报道，Aurora-A的过表达和表皮生长因子（EGF）受体（EGFR）的组成性激活与染色体不稳定性有关。在这项研究中，我们研究了当用EGF处理细胞时，导致中心体扩增和微管紊乱，这对遗传不稳定性至关重要。有趣的是，EGF刺激也增加了Aurora-A的表达。免疫荧光检测显示EGF可诱导EGFR核转位。染色质免疫沉淀（ChIP）和re-ChIP检测显示，EGF诱导的细胞核EGFR和信号转导和转录激活因子5（STAT 5）的Aurora-A启动子的招募显着。免疫共沉淀试验进一步证明EGF诱导EGFR和STAT 5之间的核相互作用。小干扰（si）RNA敲低试验也表明，EGFR和STAT 5确实参与EGF增加的Aurora-A基因表达。总之，这项研究提出，核EGFR与STAT 5结合并增加Aurora-A基因表达，最终可能导致染色体不稳定和肿瘤发生。这些结果还提供了EGFR信号通路与肿瘤发生和染色体不稳定性中Aurora-A过表达之间的新联系。
Loss of the maintenance of genetic material is a critical step leading to tumorigenesis. It was reported that overexpression of Aurora-A and the constitutive activation of the epidermal growth factor (EGF) receptor (EGFR) are implicated in chromosome instability. In this study, we examined that when cells treated with EGF result in centrosome amplification and microtubule disorder, which are critical for genetic instability. Interestingly, the expression of Aurora-A was also increased by EGF stimulus. An immunofluorescence assay indicated that EGF can induce the nuclear translocation of EGFR. Chromatin immunoprecipitation (ChIP) and re-ChIP assays showed significant EGF-induced recruitment of nuclear EGFR and signal transducer and activator of transcription 5 (STAT5) to the Aurora-A promoter. A co-immunoprecipitation assay further demonstrated that EGF induces nuclear interaction between EGFR and STAT5. A small interfering (si)RNA knockdown assay also showed that EGFR and STAT5 are indeed involved in EGF-increased Aurora-A gene expression. Altogether, this study proposes that the nuclear EGFR associates with STAT5 to bind and increase Aurora-A gene expression, which ultimately may lead to chromosome instability and tumorigenesis. The results also provide a novel linkage between the EGFR signaling pathway and overexpression of Aurora-A in tumorigenesis and chromosome instability.
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影响因子：
56.9
作者：
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通讯作者：
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