Inhibition of gastric carcinogenesis by the hormone, gastrin, is mediated by suppression of TFF1 epigenetic silencing
Identifieur interne : 006F38 ( Main/Exploration ); précédent : 006F37; suivant : 006F39Inhibition of gastric carcinogenesis by the hormone, gastrin, is mediated by suppression of TFF1 epigenetic silencing
Auteurs : Hiroyuki Tomita [États-Unis] ; Shigeo Takaishi [États-Unis] ; Trevelyan R. Menheniott [Australie] ; Xiangdong Yang [États-Unis] ; Wataru Shibata [États-Unis] ; Guangchun Jin [États-Unis] ; Kelly S. Betz [États-Unis] ; Kazuyuki Kawakami [Japon] ; Toshinari Minamoto [Japon] ; Catherine Tomasetto ; Marie-Christine Rio ; Nataporn Lerkowit [Royaume-Uni] ; Andrea Varro [Royaume-Uni] ; Andrew S. Giraud [Australie] ; Timothy C. Wang [États-Unis]Source :
- Gastroenterology [ 0016-5085 ] ; 2010.
Abstract
Epigenetic alterations have been correlated with field cancerization in human patients, but evidence from experimental models that specific epigenetic changes can initiate cancer has been lacking. Although hormones have been associated with cancer risk, the mechanisms have not been determined. The peptide hormone, gastrin, exerts a suppressive effect on antral gastric carcinogenesis.
Human intestinal-type gastric cancers in the antrum exhibited progressive
Antral gastric cancer initiation is associated with progressive epigenetic silencing of
Url:
DOI: 10.1053/j.gastro.2010.11.037
PubMed: 21111741
PubMed Central: 3049860
Affiliations:
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Betz</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Kawakami, Kazuyuki" sort="Kawakami, Kazuyuki" uniqKey="Kawakami K" first="Kazuyuki" last="Kawakami">Kazuyuki Kawakami</name><affiliation wicri:level="1"><nlm:aff id="A3"> Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea> Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa</wicri:regionArea><wicri:noRegion>Kanazawa</wicri:noRegion></affiliation></author><author><name sortKey="Minamoto, Toshinari" sort="Minamoto, Toshinari" uniqKey="Minamoto T" first="Toshinari" last="Minamoto">Toshinari Minamoto</name><affiliation wicri:level="1"><nlm:aff id="A3"> Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea> Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa</wicri:regionArea><wicri:noRegion>Kanazawa</wicri:noRegion></affiliation></author><author><name sortKey="Tomasetto, Catherine" sort="Tomasetto, Catherine" uniqKey="Tomasetto C" first="Catherine" last="Tomasetto">Catherine Tomasetto</name><affiliation><nlm:aff id="A4"> Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur/Collège de France</nlm:aff><wicri:noCountry code="subfield">CNRS/INSERM/Université Louis Pasteur/Collège de France</wicri:noCountry></affiliation></author><author><name sortKey="Rio, Marie Christine" sort="Rio, Marie Christine" uniqKey="Rio M" first="Marie-Christine" last="Rio">Marie-Christine Rio</name><affiliation><nlm:aff id="A4"> Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur/Collège de France</nlm:aff><wicri:noCountry code="subfield">CNRS/INSERM/Université Louis Pasteur/Collège de France</wicri:noCountry></affiliation></author><author><name sortKey="Lerkowit, Nataporn" sort="Lerkowit, Nataporn" uniqKey="Lerkowit N" first="Nataporn" last="Lerkowit">Nataporn Lerkowit</name><affiliation wicri:level="1"><nlm:aff id="A5"> School of Biomedical Sciences, University of Liverpool, Liverpool, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> School of Biomedical Sciences, University of Liverpool, Liverpool</wicri:regionArea><wicri:noRegion>Liverpool</wicri:noRegion></affiliation></author><author><name sortKey="Varro, Andrea" sort="Varro, Andrea" uniqKey="Varro A" first="Andrea" last="Varro">Andrea Varro</name><affiliation wicri:level="1"><nlm:aff id="A5"> School of Biomedical Sciences, University of Liverpool, Liverpool, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> School of Biomedical Sciences, University of Liverpool, Liverpool</wicri:regionArea><wicri:noRegion>Liverpool</wicri:noRegion></affiliation></author><author><name sortKey="Giraud, Andrew S" sort="Giraud, Andrew S" uniqKey="Giraud A" first="Andrew S." last="Giraud">Andrew S. Giraud</name><affiliation wicri:level="1"><nlm:aff id="A2"> Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052</wicri:regionArea><wicri:noRegion>3052</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Timothy C" sort="Wang, Timothy C" uniqKey="Wang T" first="Timothy C." last="Wang">Timothy C. Wang</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21111741</idno><idno type="pmc">3049860</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049860</idno><idno type="RBID">PMC:3049860</idno><idno type="doi">10.1053/j.gastro.2010.11.037</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">001408</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001408</idno><idno type="wicri:Area/Pmc/Curation">001268</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001268</idno><idno type="wicri:Area/Pmc/Checkpoint">002558</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002558</idno><idno type="wicri:Area/Ncbi/Merge">000933</idno><idno type="wicri:Area/Ncbi/Curation">000933</idno><idno type="wicri:Area/Ncbi/Checkpoint">000933</idno><idno type="wicri:doubleKey">0016-5085:2010:Tomita H:inhibition:of:gastric</idno><idno type="wicri:Area/Main/Merge">007448</idno><idno type="wicri:Area/Main/Curation">006F38</idno><idno type="wicri:Area/Main/Exploration">006F38</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Inhibition of gastric carcinogenesis by the hormone, gastrin, is mediated by suppression of <italic>TFF1</italic> epigenetic silencing</title><author><name sortKey="Tomita, Hiroyuki" sort="Tomita, Hiroyuki" uniqKey="Tomita H" first="Hiroyuki" last="Tomita">Hiroyuki Tomita</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Takaishi, Shigeo" sort="Takaishi, Shigeo" uniqKey="Takaishi S" first="Shigeo" last="Takaishi">Shigeo Takaishi</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Menheniott, Trevelyan R" sort="Menheniott, Trevelyan R" uniqKey="Menheniott T" first="Trevelyan R." last="Menheniott">Trevelyan R. Menheniott</name><affiliation wicri:level="1"><nlm:aff id="A2"> Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052</wicri:regionArea><wicri:noRegion>3052</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Xiangdong" sort="Yang, Xiangdong" uniqKey="Yang X" first="Xiangdong" last="Yang">Xiangdong Yang</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Shibata, Wataru" sort="Shibata, Wataru" uniqKey="Shibata W" first="Wataru" last="Shibata">Wataru Shibata</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jin, Guangchun" sort="Jin, Guangchun" uniqKey="Jin G" first="Guangchun" last="Jin">Guangchun Jin</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Betz, Kelly S" sort="Betz, Kelly S" uniqKey="Betz K" first="Kelly S." last="Betz">Kelly S. Betz</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Kawakami, Kazuyuki" sort="Kawakami, Kazuyuki" uniqKey="Kawakami K" first="Kazuyuki" last="Kawakami">Kazuyuki Kawakami</name><affiliation wicri:level="1"><nlm:aff id="A3"> Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea> Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa</wicri:regionArea><wicri:noRegion>Kanazawa</wicri:noRegion></affiliation></author><author><name sortKey="Minamoto, Toshinari" sort="Minamoto, Toshinari" uniqKey="Minamoto T" first="Toshinari" last="Minamoto">Toshinari Minamoto</name><affiliation wicri:level="1"><nlm:aff id="A3"> Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea> Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa</wicri:regionArea><wicri:noRegion>Kanazawa</wicri:noRegion></affiliation></author><author><name sortKey="Tomasetto, Catherine" sort="Tomasetto, Catherine" uniqKey="Tomasetto C" first="Catherine" last="Tomasetto">Catherine Tomasetto</name><affiliation><nlm:aff id="A4"> Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur/Collège de France</nlm:aff><wicri:noCountry code="subfield">CNRS/INSERM/Université Louis Pasteur/Collège de France</wicri:noCountry></affiliation></author><author><name sortKey="Rio, Marie Christine" sort="Rio, Marie Christine" uniqKey="Rio M" first="Marie-Christine" last="Rio">Marie-Christine Rio</name><affiliation><nlm:aff id="A4"> Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur/Collège de France</nlm:aff><wicri:noCountry code="subfield">CNRS/INSERM/Université Louis Pasteur/Collège de France</wicri:noCountry></affiliation></author><author><name sortKey="Lerkowit, Nataporn" sort="Lerkowit, Nataporn" uniqKey="Lerkowit N" first="Nataporn" last="Lerkowit">Nataporn Lerkowit</name><affiliation wicri:level="1"><nlm:aff id="A5"> School of Biomedical Sciences, University of Liverpool, Liverpool, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> School of Biomedical Sciences, University of Liverpool, Liverpool</wicri:regionArea><wicri:noRegion>Liverpool</wicri:noRegion></affiliation></author><author><name sortKey="Varro, Andrea" sort="Varro, Andrea" uniqKey="Varro A" first="Andrea" last="Varro">Andrea Varro</name><affiliation wicri:level="1"><nlm:aff id="A5"> School of Biomedical Sciences, University of Liverpool, Liverpool, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> School of Biomedical Sciences, University of Liverpool, Liverpool</wicri:regionArea><wicri:noRegion>Liverpool</wicri:noRegion></affiliation></author><author><name sortKey="Giraud, Andrew S" sort="Giraud, Andrew S" uniqKey="Giraud A" first="Andrew S." last="Giraud">Andrew S. Giraud</name><affiliation wicri:level="1"><nlm:aff id="A2"> Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052</wicri:regionArea><wicri:noRegion>3052</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Timothy C" sort="Wang, Timothy C" uniqKey="Wang T" first="Timothy C." last="Wang">Timothy C. Wang</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Division of Digestive and Liver Disease, Irving Cancer Research Center, Department of Medicine, Columbia University Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j">Gastroenterology</title><idno type="ISSN">0016-5085</idno><idno type="eISSN">1528-0012</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background & Aims</title><p id="P2">Epigenetic alterations have been correlated with field cancerization in human patients, but evidence from experimental models that specific epigenetic changes can initiate cancer has been lacking. Although hormones have been associated with cancer risk, the mechanisms have not been determined. The peptide hormone, gastrin, exerts a suppressive effect on antral gastric carcinogenesis.</p></sec><sec sec-type="methods" id="S2"><title>Methods</title><p id="P3"><italic>N-methyl-N-nitrosourea</italic> (MNU)–dependent gastric cancer was investigated in hypergastrinemic (INS-GAS), gastrin-deficient (GAS<sup>-/-</sup>), <italic>Tff1</italic>-deficient (<italic>Tff1</italic><sup>+/-</sup>), and wild-type (WT) mice. Epigenetic alterations of the Trefoil Factor 1 <italic>(TFF1</italic>) tumor suppressor gene were evaluated <italic>in vitro</italic> and <italic>in vivo</italic>.</p></sec><sec id="S3"><title>Results</title><p id="P4">Human intestinal-type gastric cancers in the antrum exhibited progressive <italic>TFF1</italic> repression and promoter hypermethylation. Mice treated with MNU exhibited a field defect characterized by widespread <italic>Tff1</italic> repression associated with histone H3 lysine 9 (H3K9) methylation and H3 deacetylation at the <italic>Tff1</italic> promoter in epithelial cells. In MNU-induced advanced cancers, DNA methylation at the <italic>Tff1</italic> promoter was observed. Tumor induction and <italic>Tff1</italic> repression were increased in MNU-treated mice by <italic>Helicobacter</italic> infection. Hypergastrinemia suppressed MNU-dependent tumor initiation and progression in a manner that correlated with gene silencing and epigenetic alterations of <italic>Tff1</italic>. In contrast, homozygous gastrin-deficient and heterozygous <italic>Tff1</italic>-deficient mice showed enhanced MNU-dependent field defects and cancer initiation compared with WT mice. In gastric cancer cells, gastrin stimulation partially reversed the epigenetic silencing in the <italic>TFF1</italic> promoter.</p></sec><sec id="S4"><title>Conclusions</title><p id="P5">Antral gastric cancer initiation is associated with progressive epigenetic silencing of <italic>TFF1</italic>, which can be suppressed by the hormone gastrin.</p></sec></div></front></TEI><affiliations><list><country><li>Australie</li><li>Japon</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>État de New York</li></region></list><tree><noCountry><name sortKey="Rio, Marie Christine" sort="Rio, Marie Christine" uniqKey="Rio M" first="Marie-Christine" last="Rio">Marie-Christine Rio</name><name sortKey="Tomasetto, Catherine" sort="Tomasetto, Catherine" uniqKey="Tomasetto C" first="Catherine" last="Tomasetto">Catherine Tomasetto</name></noCountry><country name="États-Unis"><region name="État de New York"><name sortKey="Tomita, Hiroyuki" sort="Tomita, Hiroyuki" uniqKey="Tomita H" first="Hiroyuki" last="Tomita">Hiroyuki Tomita</name></region><name sortKey="Betz, Kelly S" sort="Betz, Kelly S" uniqKey="Betz K" first="Kelly S." last="Betz">Kelly S. Betz</name><name sortKey="Jin, Guangchun" sort="Jin, Guangchun" uniqKey="Jin G" first="Guangchun" last="Jin">Guangchun Jin</name><name sortKey="Shibata, Wataru" sort="Shibata, Wataru" uniqKey="Shibata W" first="Wataru" last="Shibata">Wataru Shibata</name><name sortKey="Takaishi, Shigeo" sort="Takaishi, Shigeo" uniqKey="Takaishi S" first="Shigeo" last="Takaishi">Shigeo Takaishi</name><name sortKey="Wang, Timothy C" sort="Wang, Timothy C" uniqKey="Wang T" first="Timothy C." last="Wang">Timothy C. Wang</name><name sortKey="Yang, Xiangdong" sort="Yang, Xiangdong" uniqKey="Yang X" first="Xiangdong" last="Yang">Xiangdong Yang</name></country><country name="Australie"><noRegion><name sortKey="Menheniott, Trevelyan R" sort="Menheniott, Trevelyan R" uniqKey="Menheniott T" first="Trevelyan R." last="Menheniott">Trevelyan R. Menheniott</name></noRegion><name sortKey="Giraud, Andrew S" sort="Giraud, Andrew S" uniqKey="Giraud A" first="Andrew S." last="Giraud">Andrew S. Giraud</name></country><country name="Japon"><noRegion><name sortKey="Kawakami, Kazuyuki" sort="Kawakami, Kazuyuki" uniqKey="Kawakami K" first="Kazuyuki" last="Kawakami">Kazuyuki Kawakami</name></noRegion><name sortKey="Minamoto, Toshinari" sort="Minamoto, Toshinari" uniqKey="Minamoto T" first="Toshinari" last="Minamoto">Toshinari Minamoto</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Lerkowit, Nataporn" sort="Lerkowit, Nataporn" uniqKey="Lerkowit N" first="Nataporn" last="Lerkowit">Nataporn Lerkowit</name></noRegion><name sortKey="Varro, Andrea" sort="Varro, Andrea" uniqKey="Varro A" first="Andrea" last="Varro">Andrea Varro</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |