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Article: Expression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: Implication of HBx in upregulation of COX-2

TitleExpression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: Implication of HBx in upregulation of COX-2
Authors
Issue Date2004
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/
Citation
Modern Pathology, 2004, v. 17 n. 10, p. 1169-1179 How to Cite?
AbstractHepatitis B virus is a major etiological factor of hepatocellular carcinoma, but the underlying mechanisms remain unclear. We have previously demonstrated that upregulation of cyclooxygenase (COX)-2 in chronic hepatitis B persisted despite successful antiviral therapy. In this study, we investigated the relationship between the transactivator HBx and COX-2 in hepatitis B virus-associated chronic liver diseases. Expressions of HBx and COX-2 in tissue specimens were determined by single and double immunohistochemistry. The effects of HBx on COX-2 and prostaglandin E 2 production were studied by transfection. HBx was expressed in 11/11 (100%) of chronic hepatitis B, 23/23 (100%) of cirrhosis, and 18/23 (78%) of hepatocellular carcinoma, whereas no immunoreactivity was found in four nonalcoholic steato-hepatitis controls. COX-2 expression was also detected in all specimens of liver lesions except in only 29% of poorly differentiated hepatocellular carcinoma. Significant correlation between HBx and COX-2 immunoreactivity scores was found in different types of chronic liver diseases (chronic hepatitis B, rs = 0.68; cirrhosis, rs = 0.57; hepatocellular carcinoma, rs = 0.45). Double immunohistochemistry showed colocalization of HBx and COX-2 in hepatic parenchymal cells. Similar to COX-2, there was no significant change in HBx expression in patients with chronic hepatitis B after interferon and lamivudine therapy when hepatitis B virus DNA became undetectable and inflammation subsided. Transfection of Hep3B hepatocellular carcinoma cells with HBx increased COX-2 expression and prostaglandin E 2 production. HBx was localized mainly in the cytoplasm and less in nucleus, as found in the liver lesions. In conclusion, our results strongly suggested that there was a close relationship between HBx and COX-2. COX-2 might represent an important cellular effector of HBx that contributes to hepatitis B virus-associated hepatocarcinogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/163185
ISSN
2015 Impact Factor: 5.485
2015 SCImago Journal Rankings: 2.803
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheng, ASLen_US
dc.contributor.authorChan, HLYen_US
dc.contributor.authorLeung, WKen_US
dc.contributor.authorTo, KFen_US
dc.contributor.authorGo, MYYen_US
dc.contributor.authorChan, JYHen_US
dc.contributor.authorLiew, CTen_US
dc.contributor.authorSung, JJYen_US
dc.date.accessioned2012-09-05T05:28:30Z-
dc.date.available2012-09-05T05:28:30Z-
dc.date.issued2004en_US
dc.identifier.citationModern Pathology, 2004, v. 17 n. 10, p. 1169-1179en_US
dc.identifier.issn0893-3952en_US
dc.identifier.urihttp://hdl.handle.net/10722/163185-
dc.description.abstractHepatitis B virus is a major etiological factor of hepatocellular carcinoma, but the underlying mechanisms remain unclear. We have previously demonstrated that upregulation of cyclooxygenase (COX)-2 in chronic hepatitis B persisted despite successful antiviral therapy. In this study, we investigated the relationship between the transactivator HBx and COX-2 in hepatitis B virus-associated chronic liver diseases. Expressions of HBx and COX-2 in tissue specimens were determined by single and double immunohistochemistry. The effects of HBx on COX-2 and prostaglandin E 2 production were studied by transfection. HBx was expressed in 11/11 (100%) of chronic hepatitis B, 23/23 (100%) of cirrhosis, and 18/23 (78%) of hepatocellular carcinoma, whereas no immunoreactivity was found in four nonalcoholic steato-hepatitis controls. COX-2 expression was also detected in all specimens of liver lesions except in only 29% of poorly differentiated hepatocellular carcinoma. Significant correlation between HBx and COX-2 immunoreactivity scores was found in different types of chronic liver diseases (chronic hepatitis B, rs = 0.68; cirrhosis, rs = 0.57; hepatocellular carcinoma, rs = 0.45). Double immunohistochemistry showed colocalization of HBx and COX-2 in hepatic parenchymal cells. Similar to COX-2, there was no significant change in HBx expression in patients with chronic hepatitis B after interferon and lamivudine therapy when hepatitis B virus DNA became undetectable and inflammation subsided. Transfection of Hep3B hepatocellular carcinoma cells with HBx increased COX-2 expression and prostaglandin E 2 production. HBx was localized mainly in the cytoplasm and less in nucleus, as found in the liver lesions. In conclusion, our results strongly suggested that there was a close relationship between HBx and COX-2. COX-2 might represent an important cellular effector of HBx that contributes to hepatitis B virus-associated hepatocarcinogenesis.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/en_US
dc.relation.ispartofModern Pathologyen_US
dc.subject.meshAnti-Hiv Agents - Therapeutic Useen_US
dc.subject.meshCarcinoma, Hepatocellular - Metabolism - Pathologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCyclooxygenase 2en_US
dc.subject.meshDinoprostone - Metabolismen_US
dc.subject.meshGreen Fluorescent Proteins - Genetics - Metabolismen_US
dc.subject.meshHepatitis B, Chronic - Drug Therapy - Metabolism - Pathologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshInterferons - Therapeutic Useen_US
dc.subject.meshIsoenzymes - Biosynthesis - Geneticsen_US
dc.subject.meshLamivudine - Therapeutic Useen_US
dc.subject.meshLiver Cirrhosis - Metabolism - Pathologyen_US
dc.subject.meshLiver Diseases - Metabolism - Pathologyen_US
dc.subject.meshLiver Neoplasms - Metabolism - Pathologyen_US
dc.subject.meshMembrane Proteinsen_US
dc.subject.meshMicroscopy, Fluorescenceen_US
dc.subject.meshPlasmids - Geneticsen_US
dc.subject.meshProstaglandin-Endoperoxide Synthases - Biosynthesis - Geneticsen_US
dc.subject.meshRna, Messenger - Genetics - Metabolismen_US
dc.subject.meshRecombinant Fusion Proteins - Genetics - Metabolismen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTrans-Activators - Biosynthesis - Geneticsen_US
dc.subject.meshTransfectionen_US
dc.titleExpression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: Implication of HBx in upregulation of COX-2en_US
dc.typeArticleen_US
dc.identifier.emailLeung, WK:waikleung@hku.hken_US
dc.identifier.authorityLeung, WK=rp01479en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/modpathol.3800196en_US
dc.identifier.pmid15218507-
dc.identifier.scopuseid_2-s2.0-4744351642en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-4744351642&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume17en_US
dc.identifier.issue10en_US
dc.identifier.spage1169en_US
dc.identifier.epage1179en_US
dc.identifier.isiWOS:000224094600001-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridCheng, ASL=7402075036en_US
dc.identifier.scopusauthoridChan, HLY=16038785900en_US
dc.identifier.scopusauthoridLeung, WK=7201504523en_US
dc.identifier.scopusauthoridTo, KF=7101911940en_US
dc.identifier.scopusauthoridGo, MYY=7101882939en_US
dc.identifier.scopusauthoridChan, JYH=27168376500en_US
dc.identifier.scopusauthoridLiew, CT=35809476000en_US
dc.identifier.scopusauthoridSung, JJY=35405352400en_US

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