Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma
Background and aimsMechanisms of the progression from Barrett's oesophagus to oesophageal adenocarcinoma (OA) are not fully understood. Bile acids may have an important role in this progression. This study aimed at examining the role of NADPH oxidase NOX5-S and a novel bile acid receptor TGR5 i...
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| Veröffentlicht in: | Gut 2010-02, Vol.59 (2), p.170-180 |
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| creator | Hong, Jie Behar, Jose Wands, Jack Resnick, Murray Wang, Li Juan DeLellis, Ronald A Lambeth, David Souza, Rhonda F Spechler, Stuart J Cao, Weibiao |
| description | Background and aimsMechanisms of the progression from Barrett's oesophagus to oesophageal adenocarcinoma (OA) are not fully understood. Bile acids may have an important role in this progression. This study aimed at examining the role of NADPH oxidase NOX5-S and a novel bile acid receptor TGR5 in taurodeoxycholic acid (TDCA)-induced increase in cell proliferation.MethodsHuman Barrett's cell line BAR-T and OA cell line FLO were transfected by the Lipofectamine 2000 or Amaxa-Nucleofector-System. mRNAs were measured by real-time PCR. H2O2 was measured by a fluorescent assay. Cell proliferation was determined by measurement of thymidine incorporation.ResultsNOX5-S was present in FLO cells. TDCA significantly increased NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. This increase in thymidine incorporation was significantly reduced by knockdown of NOX5-S. TGR5 mRNA and protein levels were significantly higher in OA tissues than in normal oesophageal mucosa or Barrett's mucosa. Knockdown of TGR5 markedly inhibited TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. Overexpression of TGR5 significantly enhanced the effects of TDCA in FLO cells. TGR5 receptors were coupled with Gαq and Gαi3 proteins, but only Gαq mediated TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO cells.ConclusionsTDCA-induced increase in cell proliferation depends on upregulation of NOX5-S expression in BAR-T and FLO cells. TDCA-induced NOX5-S expression may be mediated by activation of the TGR5 receptor and Gαq protein. These data may provide potential targets to prevent and/or treat Barrett's OA. |
| doi_str_mv | 10.1136/gut.2009.188375 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3049934</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4014285811</sourcerecordid><originalsourceid>FETCH-LOGICAL-b589t-edbde39b7f5b31d585e2c12a6f3b52a6543700401b16d59b4c8c874a44a327083</originalsourceid><addsrcrecordid>eNqFkctvEzEQxi1ERdPCmRuyhLhU2tTPtX1BqqI2VKp4lPAQF8v2epMNu-vF3lTw3-NoowAnTqPR_OabT_MB8ByjOca0vFzvxjlBSM2xlFTwR2CGWSkLSqR8DGYIYVFwwdQpOEtpixCSUuEn4BQrRcoSixn4eh9aD0MNDezDg2-hbXJvXFPB6J0fxhDhannPYdPDceNh5TMUhs73434r-BSGjVl700JT-T44E13Th848BSe1aZN_dqjn4NPN9Wrxprh7t7xdXN0Vlks1Fr6ylafKippbiisuuScOE1PW1PJcOKMCIYawxWXFlWVOOimYYcxQIpCk5-D1pDvsbOcrl41F0-ohNp2Jv3Qwjf530jcbvQ4PmiKmFGVZ4OVBIIYfO59GvQ272GfPGguRCcEIz9TlRLkYUoq-Pl7ASO-j0DkKvY9CT1HkjRd_G_vDH36fgVcHwCRn2jqa3jXpyBFCS8nlnismrkmj_3mcm_hdlyJf0m8_LzR_jz4uVx--6G-Zv5h4223_6_I3GwWuXw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1779347425</pqid></control><display><type>article</type><title>Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma</title><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><source>PubMed Central</source><creator>Hong, Jie ; Behar, Jose ; Wands, Jack ; Resnick, Murray ; Wang, Li Juan ; DeLellis, Ronald A ; Lambeth, David ; Souza, Rhonda F ; Spechler, Stuart J ; Cao, Weibiao</creator><creatorcontrib>Hong, Jie ; Behar, Jose ; Wands, Jack ; Resnick, Murray ; Wang, Li Juan ; DeLellis, Ronald A ; Lambeth, David ; Souza, Rhonda F ; Spechler, Stuart J ; Cao, Weibiao</creatorcontrib><description>Background and aimsMechanisms of the progression from Barrett's oesophagus to oesophageal adenocarcinoma (OA) are not fully understood. Bile acids may have an important role in this progression. This study aimed at examining the role of NADPH oxidase NOX5-S and a novel bile acid receptor TGR5 in taurodeoxycholic acid (TDCA)-induced increase in cell proliferation.MethodsHuman Barrett's cell line BAR-T and OA cell line FLO were transfected by the Lipofectamine 2000 or Amaxa-Nucleofector-System. mRNAs were measured by real-time PCR. H2O2 was measured by a fluorescent assay. Cell proliferation was determined by measurement of thymidine incorporation.ResultsNOX5-S was present in FLO cells. TDCA significantly increased NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. This increase in thymidine incorporation was significantly reduced by knockdown of NOX5-S. TGR5 mRNA and protein levels were significantly higher in OA tissues than in normal oesophageal mucosa or Barrett's mucosa. Knockdown of TGR5 markedly inhibited TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. Overexpression of TGR5 significantly enhanced the effects of TDCA in FLO cells. TGR5 receptors were coupled with Gαq and Gαi3 proteins, but only Gαq mediated TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO cells.ConclusionsTDCA-induced increase in cell proliferation depends on upregulation of NOX5-S expression in BAR-T and FLO cells. TDCA-induced NOX5-S expression may be mediated by activation of the TGR5 receptor and Gαq protein. These data may provide potential targets to prevent and/or treat Barrett's OA.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gut.2009.188375</identifier><identifier>PMID: 19926617</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>5-RACE ; Adenocarcinoma - etiology ; Adenocarcinoma - metabolism ; Antibiotics ; Barrett's carcinoma ; Barrett's oesophagus ; Bile ; bile acid ; Bile acid receptor ; Biological and medical sciences ; Cell growth ; Cholagogues and Choleretics ; CREB ; cyclic AMP response element binding protein ; Deoxyribonucleic acid ; DNA ; DNA damage ; esophageal adenocarcinoma ; Esophageal Neoplasms - etiology ; Esophageal Neoplasms - metabolism ; Esophagus ; G protein-coupled bile acid receptor 1 ; G proteins ; Gastroenterology. Liver. Pancreas. Abdomen ; Gastroesophageal reflux ; Gene Expression Regulation - drug effects ; Gene Knockdown Techniques ; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism ; H2O2 ; Humans ; hydrogen peroxide ; Kinases ; Medical sciences ; Membrane Proteins - metabolism ; Metabolism ; NADPH oxidase ; NADPH Oxidase 5 ; NADPH Oxidases - metabolism ; NAPDH oxidase short form ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Neoplasm Proteins - physiology ; NOX5-S ; oesophageal adenocarcinoma ; Oxidative stress ; PPI ; Proteins ; proton pump inhibitors ; rapid amplification of 5' complementary DNA ends ; reactive oxygen species ; Reactive Oxygen Species - metabolism ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; Receptors, G-Protein-Coupled - physiology ; Reverse Transcriptase Polymerase Chain Reaction - methods ; RNA, Messenger - genetics ; Rodents ; ROS ; siRNA ; small interfering RNA ; Taurodeoxycholic Acid ; TDCA ; TGR5 ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Gut, 2010-02, Vol.59 (2), p.170-180</ispartof><rights>2009, Published by the BMJ Publishing Group Limited For permission to use, (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright: 2009 (c) 2009, Published by the BMJ Publishing Group Limited For permission to use, (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b589t-edbde39b7f5b31d585e2c12a6f3b52a6543700401b16d59b4c8c874a44a327083</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://gut.bmj.com/content/59/2/170.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://gut.bmj.com/content/59/2/170.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,230,314,723,776,780,881,3183,23550,27901,27902,53766,53768,77342,77373</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22368587$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19926617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hong, Jie</creatorcontrib><creatorcontrib>Behar, Jose</creatorcontrib><creatorcontrib>Wands, Jack</creatorcontrib><creatorcontrib>Resnick, Murray</creatorcontrib><creatorcontrib>Wang, Li Juan</creatorcontrib><creatorcontrib>DeLellis, Ronald A</creatorcontrib><creatorcontrib>Lambeth, David</creatorcontrib><creatorcontrib>Souza, Rhonda F</creatorcontrib><creatorcontrib>Spechler, Stuart J</creatorcontrib><creatorcontrib>Cao, Weibiao</creatorcontrib><title>Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma</title><title>Gut</title><addtitle>Gut</addtitle><description>Background and aimsMechanisms of the progression from Barrett's oesophagus to oesophageal adenocarcinoma (OA) are not fully understood. Bile acids may have an important role in this progression. This study aimed at examining the role of NADPH oxidase NOX5-S and a novel bile acid receptor TGR5 in taurodeoxycholic acid (TDCA)-induced increase in cell proliferation.MethodsHuman Barrett's cell line BAR-T and OA cell line FLO were transfected by the Lipofectamine 2000 or Amaxa-Nucleofector-System. mRNAs were measured by real-time PCR. H2O2 was measured by a fluorescent assay. Cell proliferation was determined by measurement of thymidine incorporation.ResultsNOX5-S was present in FLO cells. TDCA significantly increased NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. This increase in thymidine incorporation was significantly reduced by knockdown of NOX5-S. TGR5 mRNA and protein levels were significantly higher in OA tissues than in normal oesophageal mucosa or Barrett's mucosa. Knockdown of TGR5 markedly inhibited TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. Overexpression of TGR5 significantly enhanced the effects of TDCA in FLO cells. TGR5 receptors were coupled with Gαq and Gαi3 proteins, but only Gαq mediated TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO cells.ConclusionsTDCA-induced increase in cell proliferation depends on upregulation of NOX5-S expression in BAR-T and FLO cells. TDCA-induced NOX5-S expression may be mediated by activation of the TGR5 receptor and Gαq protein. These data may provide potential targets to prevent and/or treat Barrett's OA.</description><subject>5-RACE</subject><subject>Adenocarcinoma - etiology</subject><subject>Adenocarcinoma - metabolism</subject><subject>Antibiotics</subject><subject>Barrett's carcinoma</subject><subject>Barrett's oesophagus</subject><subject>Bile</subject><subject>bile acid</subject><subject>Bile acid receptor</subject><subject>Biological and medical sciences</subject><subject>Cell growth</subject><subject>Cholagogues and Choleretics</subject><subject>CREB</subject><subject>cyclic AMP response element binding protein</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>esophageal adenocarcinoma</subject><subject>Esophageal Neoplasms - etiology</subject><subject>Esophageal Neoplasms - metabolism</subject><subject>Esophagus</subject><subject>G protein-coupled bile acid receptor 1</subject><subject>G proteins</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gastroesophageal reflux</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Knockdown Techniques</subject><subject>GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism</subject><subject>H2O2</subject><subject>Humans</subject><subject>hydrogen peroxide</subject><subject>Kinases</subject><subject>Medical sciences</subject><subject>Membrane Proteins - metabolism</subject><subject>Metabolism</subject><subject>NADPH oxidase</subject><subject>NADPH Oxidase 5</subject><subject>NADPH Oxidases - metabolism</subject><subject>NAPDH oxidase short form</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplasm Proteins - physiology</subject><subject>NOX5-S</subject><subject>oesophageal adenocarcinoma</subject><subject>Oxidative stress</subject><subject>PPI</subject><subject>Proteins</subject><subject>proton pump inhibitors</subject><subject>rapid amplification of 5' complementary DNA ends</subject><subject>reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Receptors, G-Protein-Coupled - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>RNA, Messenger - genetics</subject><subject>Rodents</subject><subject>ROS</subject><subject>siRNA</subject><subject>small interfering RNA</subject><subject>Taurodeoxycholic Acid</subject><subject>TDCA</subject><subject>TGR5</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkctvEzEQxi1ERdPCmRuyhLhU2tTPtX1BqqI2VKp4lPAQF8v2epMNu-vF3lTw3-NoowAnTqPR_OabT_MB8ByjOca0vFzvxjlBSM2xlFTwR2CGWSkLSqR8DGYIYVFwwdQpOEtpixCSUuEn4BQrRcoSixn4eh9aD0MNDezDg2-hbXJvXFPB6J0fxhDhannPYdPDceNh5TMUhs73434r-BSGjVl700JT-T44E13Th848BSe1aZN_dqjn4NPN9Wrxprh7t7xdXN0Vlks1Fr6ylafKippbiisuuScOE1PW1PJcOKMCIYawxWXFlWVOOimYYcxQIpCk5-D1pDvsbOcrl41F0-ohNp2Jv3Qwjf530jcbvQ4PmiKmFGVZ4OVBIIYfO59GvQ272GfPGguRCcEIz9TlRLkYUoq-Pl7ASO-j0DkKvY9CT1HkjRd_G_vDH36fgVcHwCRn2jqa3jXpyBFCS8nlnismrkmj_3mcm_hdlyJf0m8_LzR_jz4uVx--6G-Zv5h4223_6_I3GwWuXw</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Hong, Jie</creator><creator>Behar, Jose</creator><creator>Wands, Jack</creator><creator>Resnick, Murray</creator><creator>Wang, Li Juan</creator><creator>DeLellis, Ronald A</creator><creator>Lambeth, David</creator><creator>Souza, Rhonda F</creator><creator>Spechler, Stuart J</creator><creator>Cao, Weibiao</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ Publishing Group</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20100201</creationdate><title>Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma</title><author>Hong, Jie ; Behar, Jose ; Wands, Jack ; Resnick, Murray ; Wang, Li Juan ; DeLellis, Ronald A ; Lambeth, David ; Souza, Rhonda F ; Spechler, Stuart J ; Cao, Weibiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b589t-edbde39b7f5b31d585e2c12a6f3b52a6543700401b16d59b4c8c874a44a327083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>5-RACE</topic><topic>Adenocarcinoma - etiology</topic><topic>Adenocarcinoma - metabolism</topic><topic>Antibiotics</topic><topic>Barrett's carcinoma</topic><topic>Barrett's oesophagus</topic><topic>Bile</topic><topic>bile acid</topic><topic>Bile acid receptor</topic><topic>Biological and medical sciences</topic><topic>Cell growth</topic><topic>Cholagogues and Choleretics</topic><topic>CREB</topic><topic>cyclic AMP response element binding protein</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>esophageal adenocarcinoma</topic><topic>Esophageal Neoplasms - etiology</topic><topic>Esophageal Neoplasms - metabolism</topic><topic>Esophagus</topic><topic>G protein-coupled bile acid receptor 1</topic><topic>G proteins</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gastroesophageal reflux</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Knockdown Techniques</topic><topic>GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism</topic><topic>H2O2</topic><topic>Humans</topic><topic>hydrogen peroxide</topic><topic>Kinases</topic><topic>Medical sciences</topic><topic>Membrane Proteins - metabolism</topic><topic>Metabolism</topic><topic>NADPH oxidase</topic><topic>NADPH Oxidase 5</topic><topic>NADPH Oxidases - metabolism</topic><topic>NAPDH oxidase short form</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplasm Proteins - physiology</topic><topic>NOX5-S</topic><topic>oesophageal adenocarcinoma</topic><topic>Oxidative stress</topic><topic>PPI</topic><topic>Proteins</topic><topic>proton pump inhibitors</topic><topic>rapid amplification of 5' complementary DNA ends</topic><topic>reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Receptors, G-Protein-Coupled - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction - methods</topic><topic>RNA, Messenger - genetics</topic><topic>Rodents</topic><topic>ROS</topic><topic>siRNA</topic><topic>small interfering RNA</topic><topic>Taurodeoxycholic Acid</topic><topic>TDCA</topic><topic>TGR5</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hong, Jie</creatorcontrib><creatorcontrib>Behar, Jose</creatorcontrib><creatorcontrib>Wands, Jack</creatorcontrib><creatorcontrib>Resnick, Murray</creatorcontrib><creatorcontrib>Wang, Li Juan</creatorcontrib><creatorcontrib>DeLellis, Ronald A</creatorcontrib><creatorcontrib>Lambeth, David</creatorcontrib><creatorcontrib>Souza, Rhonda F</creatorcontrib><creatorcontrib>Spechler, Stuart J</creatorcontrib><creatorcontrib>Cao, Weibiao</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hong, Jie</au><au>Behar, Jose</au><au>Wands, Jack</au><au>Resnick, Murray</au><au>Wang, Li Juan</au><au>DeLellis, Ronald A</au><au>Lambeth, David</au><au>Souza, Rhonda F</au><au>Spechler, Stuart J</au><au>Cao, Weibiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>59</volume><issue>2</issue><spage>170</spage><epage>180</epage><pages>170-180</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><coden>GUTTAK</coden><abstract>Background and aimsMechanisms of the progression from Barrett's oesophagus to oesophageal adenocarcinoma (OA) are not fully understood. Bile acids may have an important role in this progression. This study aimed at examining the role of NADPH oxidase NOX5-S and a novel bile acid receptor TGR5 in taurodeoxycholic acid (TDCA)-induced increase in cell proliferation.MethodsHuman Barrett's cell line BAR-T and OA cell line FLO were transfected by the Lipofectamine 2000 or Amaxa-Nucleofector-System. mRNAs were measured by real-time PCR. H2O2 was measured by a fluorescent assay. Cell proliferation was determined by measurement of thymidine incorporation.ResultsNOX5-S was present in FLO cells. TDCA significantly increased NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. This increase in thymidine incorporation was significantly reduced by knockdown of NOX5-S. TGR5 mRNA and protein levels were significantly higher in OA tissues than in normal oesophageal mucosa or Barrett's mucosa. Knockdown of TGR5 markedly inhibited TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. Overexpression of TGR5 significantly enhanced the effects of TDCA in FLO cells. TGR5 receptors were coupled with Gαq and Gαi3 proteins, but only Gαq mediated TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO cells.ConclusionsTDCA-induced increase in cell proliferation depends on upregulation of NOX5-S expression in BAR-T and FLO cells. TDCA-induced NOX5-S expression may be mediated by activation of the TGR5 receptor and Gαq protein. These data may provide potential targets to prevent and/or treat Barrett's OA.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>19926617</pmid><doi>10.1136/gut.2009.188375</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Gut, 2010-02, Vol.59 (2), p.170-180 |
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| source | MEDLINE; BMJ Journals - NESLi2; PubMed Central |
| subjects | 5-RACE Adenocarcinoma - etiology Adenocarcinoma - metabolism Antibiotics Barrett's carcinoma Barrett's oesophagus Bile bile acid Bile acid receptor Biological and medical sciences Cell growth Cholagogues and Choleretics CREB cyclic AMP response element binding protein Deoxyribonucleic acid DNA DNA damage esophageal adenocarcinoma Esophageal Neoplasms - etiology Esophageal Neoplasms - metabolism Esophagus G protein-coupled bile acid receptor 1 G proteins Gastroenterology. Liver. Pancreas. Abdomen Gastroesophageal reflux Gene Expression Regulation - drug effects Gene Knockdown Techniques GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism H2O2 Humans hydrogen peroxide Kinases Medical sciences Membrane Proteins - metabolism Metabolism NADPH oxidase NADPH Oxidase 5 NADPH Oxidases - metabolism NAPDH oxidase short form Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Neoplasm Proteins - physiology NOX5-S oesophageal adenocarcinoma Oxidative stress PPI Proteins proton pump inhibitors rapid amplification of 5' complementary DNA ends reactive oxygen species Reactive Oxygen Species - metabolism Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism Receptors, G-Protein-Coupled - physiology Reverse Transcriptase Polymerase Chain Reaction - methods RNA, Messenger - genetics Rodents ROS siRNA small interfering RNA Taurodeoxycholic Acid TDCA TGR5 Tumor Cells, Cultured Tumors |
| title | Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T17%3A15%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Role%20of%20a%20novel%20bile%20acid%20receptor%20TGR5%20in%20the%20development%20of%20oesophageal%20adenocarcinoma&rft.jtitle=Gut&rft.au=Hong,%20Jie&rft.date=2010-02-01&rft.volume=59&rft.issue=2&rft.spage=170&rft.epage=180&rft.pages=170-180&rft.issn=0017-5749&rft.eissn=1468-3288&rft.coden=GUTTAK&rft_id=info:doi/10.1136/gut.2009.188375&rft_dat=%3Cproquest_pubme%3E4014285811%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1779347425&rft_id=info:pmid/19926617&rfr_iscdi=true |