BACKGROUND/AIMS: Hepatitis B virus (HBV) is the etiological factor for hepatocellular carcinoma (HCC). Numerous evidence has indicated a link between chronic infection with HBV and the development of HCC. Among the four proteins encoded by HBV, Hepatitis B virus X gene(HBx), best characterized as a transcriptional transactivator, gained attention owing to its presumptive role in oncogenesis. Further, HBx has been shown to stimulate signal transduction pathways such as Ras-MAPK pathway, NF-kappaB, and Src kinase. The pleiotropic events caused by HBx may be the key to understanding the HBV-mediated oncogenicity. However, the specific roles of HBx in oncogenesis remain largely elusive. To explore the role of HBx in hepatocarcinogenesis, we examined the deregulation of host genes induced by HBx expression. METHODS: HBx was ectopically expressed in HepG2 cells using a recombinant adenovirus to transiently express HBx. Gene expression profiling of HBx was conducted on cDNA microarrays that contained 1,028 cDNAs. RESULTS: A number of oncogenes and genes that are involved in cell growth, DNA repair, cell cycle regulation, and cell motility were deregulated by HBx. CONCLUSIONS: Theses results suggest that HBx regulates transcription in a way that contributes to the proliferation of hepatocytes, a probable early event of HCC.
Carcinoma, Hepatocellular/*virology ; Cell Line, Tumor ; English Abstract ; *Gene Expression Profiling ; Gene Expression Regulation ; Genes, Viral/*physiology ; Genetic Vectors ; Hepatitis B Antigens/genetics ; Hepatitis B Virus/*genetics ; Human ; Liver Neoplasms/*virology ; Oligonucleotide Array Sequence Analysis ; Trans-Activators/*genetics/physiology

To evaluate the clinical feasibility of the antibody titer against a chimeric polypeptide (named Core 518), in which a domain of Core and NS3 of hepatitis C virus (HCV) was fused, ELISA was performed in a total of 76 serum samples. Each serum was serially diluted using two-fold dilution method with distilled water into 10 concentrations. They were all positive for second generation anti-HCV assay (HCV EIA II; Abbott Laboratories). Genotyping RT-PCR, quantitative competitive RT-PCR, and RIBA (Lucky Confirm; LG Biotech) were also assayed. Anti-Core 518 antibody was detected in x 12800 or higher dilutions of sera from 35 of 43 chronic hepatitis C (81.4%) and nine of 16 hepatocellular carcinoma sera (56.3%), one of four cirrhosis (25%), 0 of four acute hepatitis C, and one of nine healthy isolated anti-HCV-positive subjects (p=0.0000). The anti-Core 518 antibody titers were well correlated with the presence of HCV RNA in serum (p=0.002). The anti-Core 518 antibody titers decreased significantly in nine of ten responders to IFN-alpha treatment. Monitoring anti-Core 518 titers may be helpful not only for differentiating the status of HCV infection among patients with various type C viral liver diseases, but also for predicting responses to IFN-alpha treatment.
Adult ; Aged ; Female ; Genotype ; Hepatitis C/immunology* ; Hepatitis C/drug therapy* ; Hepatitis C/diagnosis ; Hepatitis C/blood ; Hepatitis C Antibodies/immunology* ; Hepatitis C Antibodies/blood ; Hepatitis C Antigens/immunology* ; Hepatitis C-Like Viruses/immunology* ; Hepatitis C-Like Viruses/genetics ; Human ; Immunoblotting ; Interferon Alfa-2a/therapeutic use* ; Male ; Middle Age ; RNA, Viral/blood ; Recombinant Fusion Proteins/immunology ; Viral Core Proteins/immunology* ; Viral Nonstructural Proteins/immunology*