title: Expression of integrated hepatitis B virus X variants in human hepatocellular carcinomas and its significance.
abstract: Hepatitis B virus X protein (HBX) has been implicated in the transactivation of diverse cellular genes and possibly also the pathogenesis of human hepatocellular carcinoma (HCC). We report the characterization of HBX variants from HBV-related human hepatocellular carcinoma (HCC). These HBX variants were integrated into the host chromosomes and also expressed in the HCC tissues. In addition, we report a novel in vitro HBX activity assay based on color changes that were indicative of the beta-galactosidase enzyme activity. Conducted in wheat germ lysates, the transactivating function of either wild type or mutant HBX protein was measured through their interaction with the Early Growth Response factor 1 (Egr-1) that controls the beta-galactosidase gene. Further analysis of these HBX deletion mutants using this assay may shed new insights on the significance of various mutations occurring in HCC-associated HBX.
authors.affiliation: Department of Clinical Research, Singapore General Hospital, Singapore, 169608, Republic of Singapore. gcrcwn@sgh.gov.sg
authors.forename: W N
authors.initials: WN
authors.lastname: Chen
authors.forename: C J
authors.initials: CJ
authors.lastname: Oon
authors.forename: A L
authors.initials: AL
authors.lastname: Leong
authors.forename: S
authors.initials: S
authors.lastname: Koh
authors.forename: S W
authors.initials: SW
authors.lastname: Teng
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology*; D002457:Cell Extracts; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051766:Early Growth Response Protein 1; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D015534:Trans-Activators / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins; D016662:Virus Integration
chemical_list: D002457:Cell Extracts; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein