Document Detail

Expression of bile acid receptor TGR5 in gastric adenocarcinoma.
MedLine Citation:
PMID:  23238937     Owner:  NLM     Status:  MEDLINE    
Bile reflux is a risk factor in the development of intestinal metaplasia in the stomach and is believed to function as an initiator of gastric carcinogenesis. However, whether the G protein-coupled bile acid receptor TGR5 is expressed in this tumor is not known. In this study, we determined the expression of TGR5 in gastric adenocarcinoma and examined the role of TGR5 in cell proliferation. Strong TGR5 staining was present in 12% of cases of intestinal metaplasia but in no cases of normal gastric epithelium (P < 0.01). Moderate to strong TGR5 membranous and cytoplasmic staining was present in 52% of the intestinal but in only 25% of the diffuse subtype of adenocarcinomas (P < 0.001). Kaplan-Meier univariate survival analysis revealed that moderate to strong TGR5 staining was associated with decreased patient survival (P < 0.05). Treatment with taurodeoxycholic acid (TDCA, a bile acid) significantly increased thymidine incorporation in the AGS gastric adenocarcinoma cell line, suggesting that bile acids may increase cell proliferation. This increase was significantly decreased by knockdown of TGR5 with TGR5 small-interfering RNA (siRNA). In addition, overexpression of TGR5 significantly enhanced TDCA-induced increases in thymidine incorporation. TGR5 is coupled with G(q)α and Gα(i-3) proteins. TDCA-induced increase in thymidine incorporation was significantly decreased by knockdown of G(q)α and Gα(i-3) with their siRNAs. We conclude that TGR5 is overexpressed in most gastric intestinal-type adenocarcinomas, and moderate to strong TGR5 staining is associated with decreased patient survival in all gastric adenocarcinomas. Bile acids increase cell proliferation via activation of TGR5 receptors and G(q)α and Gα(i-3) proteins.
Weibiao Cao; Wei Tian; Jie Hong; Dan Li; Rosemarie Tavares; Lelia Noble; Steven F Moss; Murray B Resnick
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-13
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  304     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-04-19     Revised Date:  2014-02-18    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G322-7     Citation Subset:  IM    
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MeSH Terms
Adenocarcinoma / metabolism*,  mortality
Aged, 80 and over
Cell Line, Tumor
Cell Proliferation / drug effects
Gastric Mucosa / metabolism
Middle Aged
RNA, Messenger / metabolism
RNA, Small Interfering / pharmacology
Receptors, G-Protein-Coupled / biosynthesis*
Stomach Neoplasms / metabolism*,  mortality
Survival Analysis
Taurodeoxycholic Acid / pharmacology
Thymidine / metabolism
Grant Support
Reg. No./Substance:
0/GPBAR1 protein, human; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Receptors, G-Protein-Coupled; 516-50-7/Taurodeoxycholic Acid; VC2W18DGKR/Thymidine

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