Document Detail

Helicobacter pylori CagA inhibits the expression of Runx3 via Src/MEK/ERK and p38 MAPK pathways in gastric epithelial cell.
MedLine Citation:
PMID:  22266963     Owner:  NLM     Status:  In-Data-Review    
Infection with CagA-positive Helicobacter pylori is the strongest risk factor for gastric carcinoma. Upon delivery into gastric epithelial cells, CagA disturbs cellular functions by physically interacting with and deregulating intracellular signaling molecules via both tyrosine phosphorylation-dependent and -independent mechanisms. Runx3 was suggested to be a tumor suppressor and closely associated with tumorigenesis and progression of gastric cancer. The aim of our study is to verify the effect of H. pylori virulence factor CagA on Runx3 expression level and investigate the corresponding molecular mechanisms and signaling pathways influencing Runx3 expression. Human gastric epithelial immortalized GES-1 cells were transfected with CagA-expression vector or control vector with FuGENE HD transfection reagent. Runx3 expression levels were determined by QRT-PCR and immunoblotting. Then we constructed a 1,150 bp Runx3 promoter luciferase reporter plasmid, pGL(3) -1150 bp, which was co-transfected into GES-1 cell with CagA-expression vector or control vector. Luciferase reporter assay was used to determine the effects of CagA on the 1,150 bp promoter activity of Runx3. Signal inhibitors were used to detect the signal pathway(s) through which CagA affects Runx3. Our results showed that CagA can reduce the expression level of Runx3 at both mRNA and protein levels significantly. Importantly, the 1,150 bp Runx3 promoter activity was decreased in cells transfected with CagA-expression vector comparing with cells transfected with control vector. And this inhibition is dependent on the phosphorylation of CagA. Signal pathways Src/MEK/ERK and p38 MAPK are involved in this regulation. Our findings provide new insights for understanding the mechanism of H. pylori carcinogenesis. J. Cell. Biochem. 113: 1080-1086, 2012. © 2011 Wiley Periodicals, Inc.
Zhifang Liu; Xia Xu; Long Chen; Wenjuan Li; Yundong Sun; Jiping Zeng; Han Yu; Chunyan Chen; Jihui Jia
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  113     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-01-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1080-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley Periodicals, Inc.
Department of Biochemistry and Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
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