Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.
Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.
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通过基因扩增增加 EHF 的表达有助于激活 HER 家族信号传导，并与胃癌的不良生存相关
DOI：
10.1038/cddis.2016.346
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发表时间：
2016-10-27
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
E26转化特异性（ETS）转录因子EHF/ESE-3在人类肿瘤，特别是胃癌中的生物学功能在很大程度上仍然未知。本研究旨在探讨EHF在胃癌发生中的作用及其作为胃癌治疗靶点的可能性。采用定量RT-PCR、免疫组化和荧光原位杂交技术，对胃癌组和对照组EHF的表达和拷贝数进行了研究。特异性EHF siRNA被用于确定体外和体内EHF表达改变的生物学影响和机制。采用双荧光素酶报告基因、染色质免疫沉淀（ChIP）和电泳迁移率变动分析（EMSA）鉴定其下游靶点。我们的研究结果表明，EHF显着上调，并经常在胃癌组织中扩增与对照组相比。此外，EHF扩增与其过表达呈正相关，并与胃癌患者的不良临床结局显著相关。EHF基因敲减能显著抑制胃癌细胞的增殖、集落形成、迁移、侵袭和裸鼠成瘤能力，并诱导细胞周期阻滞和凋亡。重要的是，我们确定了EHF作为一种新的HER 2转录因子和胃癌中HER 3和HER 4的调节剂。总的来说，我们的研究结果表明，EHF是一个新的功能性癌基因在胃癌中通过调节人表皮生长因子受体（HER）家族的受体酪氨酸激酶，并可能代表一个潜在的预后标志物和治疗靶点，这种癌症。
The biological function of E26 transformation-specific (ETS) transcription factor EHF/ESE-3 in human cancers remains largely unknown, particularly gastric cancer. The aim of this study was to explore the role of EHF in tumorigenesis and its potential as a therapeutic target in gastric cancer. By using quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, we investigated the expression and copy number of EHF in a cohort of gastric cancers and control subjects. Specific EHF siRNAs was used to determine the biologic impacts and mechanisms of altered EHF expression in vitro and in vivo. Dual-luciferase reporter, chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) assays were performed to identify its downstream targets. Our results demonstrated that EHF was significantly upregulated and frequently amplified in gastric cancer tissues as compared with control subjects. Moreover, EHF amplification was positively correlated with its overexpression and significantly associated with poor clinical outcomes of gastric cancer patients. We also found that EHF knockdown notably inhibited gastric cancer cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice and induced cell cycle arrest and apoptosis. Importantly, we identified EHF as a new HER2 transcription factor and the modulator of HER3 and HER4 in gastric cancer. Collectively, our findings suggest that EHF is a novel functional oncogene in gastric cancer by regulating the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases and may represent a potential prognostic marker and therapeutic target for this cancer.
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影响因子：
4.6
作者：
Cheng, Zhongping;Guo, Jing;Qu, Xiaoyan
通讯作者：
Qu, Xiaoyan
影响因子：
8
作者：
Chang, CH;Scott, GK;Benz, CC
通讯作者：
Benz, CC
基因组和生化洞察ETS转录因子的特异性。
影响因子：
16.6
作者：
Hollenhorst PC;McIntosh LP;Graves BJ
通讯作者：
Graves BJ
影响因子：
3.1
作者：
Eckel, KL;Tentler, JJ;Gutierrez-Hartmann, A
通讯作者：
Gutierrez-Hartmann, A
影响因子：
64.5
作者：
Lemmon MA;Schlessinger J
通讯作者：
Schlessinger J