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Ets1 and heat shock factor 1 regulate transcription of the Transformer 2β gene in human colon cancer cells.
MedLine Citation:
PMID:  23361474     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Transformer (Tra) 2β is a member of the serine/arginine-rich (SR)-like protein family that regulates alternative splicing of numerous genes in a concentration-dependent manner. Several types of cancer cells up-regulate Tra2β expression, while the regulatory mechanism of Tra2β expression remains to be elucidated. In this study, we examined the transcriptional regulation and possible functions of Tra2β in human colon cancer cells. METHODS: We cloned 959 bp-upstream of the human TRA2β 5'-flank into luciferase constructs. Chromatin immunoprecipitation (ChIP) was employed to identify crucial cis element(s) and trans activator(s) of the TRA2β promoter. Tra2β expression in the human colon and colon cancer tissues was examined by immunohistochemistry. RESULTS: In response to sodium arsenite, colon cancer cells (HCT116) increased levels of TRA2β1 mRNA encoding a functional, full-length Tra2β with a peak around 6 h without changing its mRNA stability. Transient expression assays using a reporter gene driven by serially truncated TRA2β promoters and Chip assay demonstrated that an Ets1-binding site present at -64 to -55 bp was crucial for basal transcription, while three heat shock elements (HSEs) located at -145 to -99 bp mediated the oxidant-induced transactivation of TRA2β. Tra2β knockdown caused apoptosis of HCT116 cells. Tra2β were preferentially expressed in proliferative compartment of normal human colonic glands and adenocarcinomas, where Ets1 and heat shock factor 1 were also highly expressed. CONCLUSIONS: Our results suggest that oxidative stress-responsive Tra2β may play an important role in colon cancer growth.
Authors:
Keisuke Kajita; Yuki Kuwano; Naruka Kitamura; Yuzuru Satake; Kensei Nishida; Ken Kurokawa; Yoko Akaike; Manami Honda; Kiyoshi Masuda; Kazuhito Rokutan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-30
Journal Detail:
Title:  Journal of gastroenterology     Volume:  -     ISSN:  1435-5922     ISO Abbreviation:  J. Gastroenterol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9430794     Medline TA:  J Gastroenterol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
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