title: Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.
abstract: 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.
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Jing
authors: J
authors: Shi
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Yiping
authors: Y
authors: Qu
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Xinru
authors: X
authors: Li
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Fang
authors: F
authors: Sui
authors: Department of Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Demao
authors: D
authors: Yao
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Qi
authors: Q
authors: Yang
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Bingyin
authors: B
authors: Shi
authors: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Meiju
authors: M
authors: Ji
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Peng
authors: P
authors: Hou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: C403306:EHF protein, human; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases