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Article: Helicobacter pylori induces promoter methylation of E-cadherin via interleukin-1β activation of nitric oxide production in gastric cancer cells

TitleHelicobacter pylori induces promoter methylation of E-cadherin via interleukin-1β activation of nitric oxide production in gastric cancer cells
Authors
KeywordsCarcinogenesis
E-Cadherin
Gastric Cancer
Helicobacter Pylori
Methylation
Issue Date2012
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
Citation
Cancer, 2012, v. 118 n. 20, p. 4969-4980 How to Cite?
AbstractBackground: Helicobacter pylori infection causes gastric mucosal inflammatory responses, resulting in up-regulation of interleukin-1β (IL-1β) and overproduction of mutagenic nitric oxide (NO). The authors previously demonstrated that IL-1β plays an important role in H. pylori-induced E-cadherin (E-cad) methylation. Here, they extend the study to investigate the downstream effect of IL-1β on H. pylori-induced gastric inflammation and aberrant DNA methylation. Methods: Human gastric cancer cell lines (MKN7, MKN74, and TMK-1) with and without pretreatment of IL-1 receptor antagonist (IL-1ra) were treated with IL-1β or infected with H. pylori. Promoter methylation status of E-cad was examined by methylation-specific polymerase chain reaction (PCR). Expression of E-cad, inducible nitric oxide synthase (iNOS), and nuclear factor κB (NFκB) was assessed by quantitative reverse transcriptase PCR, Western blotting, or immunofluorescence. NO production and total DNA methyltransferase (DNMT) activity were assayed fluorometrically. Results: Both IL-1β treatment and H. pylori infection-induced E-cad methylation led to a decrease in E-cad expression at both mRNA and protein levels. Total DNMT enzymatic activity was significantly elevated in treated cells, accounting for the observed E-cad methylation induction. Increased expression of NFκB was accompanied by up-regulation of iNOS and production of NO in treated cells. Reversal of all these phenomena in cells pretreated with IL-1ra suggested H. pylori-induced E-cad methylation via IL-1β stimulation of the NFκB transcriptional system, leading to activation of DNMT activity by NO production. Conclusions: These findings reveal a previously unknown effect of IL-1β and NO on H. pylori-induced aberrant DNA methylation. This possible pathway indicates the role of NO in epigenetic modification that links inflammation to carcinogenesis. © 2012 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/163466
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHuang, FYen_US
dc.contributor.authorChan, AOOen_US
dc.contributor.authorRashid, Aen_US
dc.contributor.authorWong, DKHen_US
dc.contributor.authorCho, CHen_US
dc.contributor.authorYuen, MFen_US
dc.date.accessioned2012-09-05T05:31:44Z-
dc.date.available2012-09-05T05:31:44Z-
dc.date.issued2012en_US
dc.identifier.citationCancer, 2012, v. 118 n. 20, p. 4969-4980en_US
dc.identifier.issn0008-543Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/163466-
dc.description.abstractBackground: Helicobacter pylori infection causes gastric mucosal inflammatory responses, resulting in up-regulation of interleukin-1β (IL-1β) and overproduction of mutagenic nitric oxide (NO). The authors previously demonstrated that IL-1β plays an important role in H. pylori-induced E-cadherin (E-cad) methylation. Here, they extend the study to investigate the downstream effect of IL-1β on H. pylori-induced gastric inflammation and aberrant DNA methylation. Methods: Human gastric cancer cell lines (MKN7, MKN74, and TMK-1) with and without pretreatment of IL-1 receptor antagonist (IL-1ra) were treated with IL-1β or infected with H. pylori. Promoter methylation status of E-cad was examined by methylation-specific polymerase chain reaction (PCR). Expression of E-cad, inducible nitric oxide synthase (iNOS), and nuclear factor κB (NFκB) was assessed by quantitative reverse transcriptase PCR, Western blotting, or immunofluorescence. NO production and total DNA methyltransferase (DNMT) activity were assayed fluorometrically. Results: Both IL-1β treatment and H. pylori infection-induced E-cad methylation led to a decrease in E-cad expression at both mRNA and protein levels. Total DNMT enzymatic activity was significantly elevated in treated cells, accounting for the observed E-cad methylation induction. Increased expression of NFκB was accompanied by up-regulation of iNOS and production of NO in treated cells. Reversal of all these phenomena in cells pretreated with IL-1ra suggested H. pylori-induced E-cad methylation via IL-1β stimulation of the NFκB transcriptional system, leading to activation of DNMT activity by NO production. Conclusions: These findings reveal a previously unknown effect of IL-1β and NO on H. pylori-induced aberrant DNA methylation. This possible pathway indicates the role of NO in epigenetic modification that links inflammation to carcinogenesis. © 2012 American Cancer Society.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_US
dc.relation.ispartofCanceren_US
dc.subjectCarcinogenesisen_US
dc.subjectE-Cadherinen_US
dc.subjectGastric Canceren_US
dc.subjectHelicobacter Pylorien_US
dc.subjectMethylationen_US
dc.titleHelicobacter pylori induces promoter methylation of E-cadherin via interleukin-1β activation of nitric oxide production in gastric cancer cellsen_US
dc.typeArticleen_US
dc.identifier.emailWong, DKH:danywong@hku.hken_US
dc.identifier.emailYuen, MF:mfyuen@hkucc.hku.hken_US
dc.identifier.authorityWong, DKH=rp00492en_US
dc.identifier.authorityYuen, MF=rp00479en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/cncr.27519en_US
dc.identifier.pmid22415887-
dc.identifier.scopuseid_2-s2.0-84867332710en_US
dc.identifier.hkuros210682-
dc.identifier.isiWOS:000310082500010-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridHuang, FY=8644138400en_US
dc.identifier.scopusauthoridChan, AOO=54927841700en_US
dc.identifier.scopusauthoridRashid, A=7102299914en_US
dc.identifier.scopusauthoridWong, DKH=7401535819en_US
dc.identifier.scopusauthoridCho, CH=35228665500en_US
dc.identifier.scopusauthoridYuen, MF=7102031955en_US

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