| Dysregulation of hepatocyte cell cycle and cell viability by hepatitis B virus. | |
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MedLine Citation:
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PMID: 19786052 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Dysregulation of the cell cycle is frequently associated with tumor development. Hepatitis B virus (HBV) is associated with a significant risk of developing hepatocellular carcinoma but the effects of HBV on cell cycle regulation are not completely understood. METHODS: We have used a recombinant adeno-HBV model system to investigate the effect of infection with HBV and the replication defective lamivudine resistant mutant rtM204I mutant on hepatocyte cell cycle and cell viability. RESULTS: Huh7 cells synchronised at the G1/S phase of the cell cycle were arrested at the G2/M following infection with rAdHBV-wt and rAdHBV-M204I. This was accompanied by increased levels of p21(cip1), p-cdc2, cyclins D, A and B. Cell viability was reduced and cleaved caspase 3 levels were increased in HBV- and rtM204I-infected cells. rAdHBV-M204I-infected Huh7 cells also demonstrated significant up-regulation of phospho-ERK, phospho-Akt, p53 and phospho-Mdm2 compared to mock-infected cells. These changes were comparable to those following infection of Huh7 cells with rAdHBV-wt. CONCLUSION: Our results suggest that HBV, regardless of phenotype, produces cell cycle arrest and reduced hepatocyte viability. Perturbations in these cellular processes are likely to underlie HBV-associated liver oncogenic transformation and may help explain the ongoing risk of developing hepatocellular carcinoma in individuals in whom the lamivudine resistant rtM204I mutant emerges. |
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Authors:
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Ruth Chin; Ulrich Nachbur; Linda Earnest-Silveira; Aleksandra Bankovacki; Bernd Koeberlein; Hanswalter Zentgraf; C-Thomas Bock; John Silke; Joseph Torresi |
Publication Detail:
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Type: Journal Article Date: 2009-09-26 |
Journal Detail:
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Title: Virus research Volume: 147 ISSN: 1872-7492 ISO Abbreviation: Virus Res. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-09 Completed Date: 2010-02-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8410979 Medline TA: Virus Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 7-16 Citation Subset: IM |
Affiliation:
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Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Victoria 3084, Australia. rchin@unimelb.edu.au |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Cycle* Cell Cycle Proteins / analysis Cell Line Cell Survival Hepatitis B virus / pathogenicity* Hepatocytes / chemistry, physiology*, virology* Humans Protein Kinases / analysis Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; EC 2.7.-/Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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