{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:57:18Z","timestamp":1790301438415,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T00:00:00Z","timestamp":1577750400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Odyssey Reinsurance Company","award":["LSHC-CT-2005-018704"],"award-info":[{"award-number":["LSHC-CT-2005-018704"]}]},{"name":"INCA Consortium\/European FP6 Program","award":["LSHC-CT-2005-018704"],"award-info":[{"award-number":["LSHC-CT-2005-018704"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Oncology"],"published-print":{"date-parts":[[2019,12,31]]},"abstract":"<jats:p><jats:italic>Helicobacter pylori<\/jats:italic> infection causes chronic gastritis and is the major risk factor of gastric cancer. <jats:italic>H. pylori<\/jats:italic> induces a chronic inflammation-producing reactive oxygen species (ROS) which is a source of chromosome instabilities and contributes to the development of malignancy. <jats:italic>H. pylori<\/jats:italic> also promotes DNA hypermethylation, known to dysregulate essential genes that maintain genetic stability. The maintenance of telomere length by telomerase is essential for chromosome integrity. Telomerase reverse transcriptase (TERT) is the catalytic component of telomerase activity and an important target during host-pathogen interaction. We aimed to investigate the consequences of <jats:italic>H. pylori<\/jats:italic> on the regulation of <jats:italic>TERT<\/jats:italic> gene expression and telomerase activity. <jats:italic>In vitro<\/jats:italic>, <jats:italic>hTERT<\/jats:italic> mRNA levels and telomerase activity were analysed in <jats:italic>H. pylori<\/jats:italic>-infected human gastric epithelial cells. In addition, C57BL\/6 and INS-GAS mice were used to investigate the influence of <jats:italic>H. pylori<\/jats:italic>-induced inflammation on TERT levels. Our data demonstrated that, <jats:italic>in vitro<\/jats:italic>, <jats:italic>H. pylori<\/jats:italic> inhibits <jats:italic>TERT<\/jats:italic> gene expression and decreases the telomerase activity. The exposure of cells to lycopene, an antioxidant compound, restores TERT levels in infected cells, indicating that ROS are implicated in this downregulation. <jats:italic>In vivo<\/jats:italic>, fewer TERT-positive cells are observed in gastric tissues of infected mice compared to uninfected, more predominantly in the vicinity of large aggregates of lymphocytes, suggesting an inflammation-mediated regulation. Furthermore, <jats:italic>H. pylori<\/jats:italic> appears to downregulate <jats:italic>TERT<\/jats:italic> gene expression through DNA hypermethylation as shown by the restoration of <jats:italic>TERT<\/jats:italic> transcript levels in cells treated with 5\u2032-azacytidine, an inhibitor of DNA methylation. This was confirmed in infected mice, by PCR-methylation assay of the <jats:italic>TERT<\/jats:italic> gene promoter. Our data unraveled a novel way for <jats:italic>H. pylori<\/jats:italic> to promote genome instabilities through the inhibition of TERT levels and telomerase activity. This mechanism could play an important role in the early steps of gastric carcinogenesis.<\/jats:p>","DOI":"10.1155\/2019\/5415761","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T18:32:54Z","timestamp":1577817174000},"page":"1-13","source":"Crossref","is-referenced-by-count":10,"title":["DNA Hypermethylation Downregulates Telomerase Reverse Transcriptase (TERT) during <i>H. pylori<\/i>-Induced Chronic Inflammation"],"prefix":"10.1155","volume":"2019","author":[{"given":"Fran\u00e7oise I.","family":"Bussi\u00e8re","sequence":"first","affiliation":[{"name":"Institut Pasteur, Unit of Helicobacter Pathogenesis, CNRS ERL6002, 25-28 Rue du Dr Roux, 75724 Paris cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Michel","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit of Helicobacter Pathogenesis, CNRS ERL6002, 25-28 Rue du Dr Roux, 75724 Paris cedex 15, 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