title: Altered expression of ETV1 and its contribution to tumorigenic phenotypes in gastrointestinal stromal tumors.
abstract: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. ETV1 is a unique transcription factor specific to GIST that has been reported to date. The present study aimed to determine aberrant ETV1 expression and its contribution to tumorigenesis in GISTs. Altered expression levels of ETV1 and its relevant signaling pathways were assessed using western blotting and quantitative real-time PCR in 72 paired patient tissue samples. In addition, immunochemistry was performed on 156 GISTs using tissue microarray to analyze the correlation between ETV1 and clinical parameters. The results revealed that ETV1 was highly expressed in the GISTs at both the transcription and protein levels. Immunochemical analysis revealed that increased expression of ETV1 was correlated with KIT in the 156 patients. In addition, the frequency of ETV1 positivity was higher when compared with KIT [50.0% (9/18) vs 38.9% (7/18)] particularly in high-risk GISTs. Analysis of western blotting data showed that total protein isoforms of Raf, MEK and ERK were similar in the GIST tissues as well as in the uninvolved normal tissues. In contrast, the level of phospho-Raf, phospho-MEK and phospho‑ERK were decreased in the tumor group. Moreover, enhanced signaling molecules such as Bcl-2 and Dvl2/GSK-3β/β-catenin/Smad2 were detected, showing a significant difference in comparison with the uninvolved normal cases. We conclude that ETV1, a member of the ETS family, is upregulated in GISTs, and its signaling is integrated into a cellular signaling network for resistance to apoptosis, tumor cell invasion and survival.
authors: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Meng-Li
authors: ML
authors: Gu
authors: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Xin-Xin
authors: XX
authors: Zhou
authors: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Han
authors: H
authors: Ma
authors: Viral Oncogenesis Section of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Hang-Ping
authors: HP
authors: Yao
authors: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors: Feng
authors: F
authors: Ji
mesh_terms: D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit