INHIBITION OF HEPATITIS-B-VIRUS CORE PROMOTER BY P53 : IMPLICATIONS FOR CARCINOGENESIS IN HEPATOCYTES

摘要: The incidence of hepatocellular carcinoma (HCC) is particularly high in regions Asia and sub-Saharan Africa where rates infection with human hepatitis-B virus (HBV) aflatoxin-B1 contamination food are high. In HCC tumors occurring inhabitants these regions, a G-to-T mutation frequently occurs at position 249 the tumor-suppressor gene p53. This suggests that HBV p53 may collaborate carcinogenic process liver. We have examined effect protein HBX lines exogenous wild-type or mutated on transactivation 2 different reporter genes. Transfection promoter from p53-responsive WAF1/p21 resulted level expression, as expected. When cells were co-transfected driven by core gene, expression was enhanced Hep 3B, HLE, PLC/PRF/5 HuH 7 lines, but not 1 line. Co-transfection plasmid containing significant inhibition all whereas had no effect. Our results indicate can inhibit transcription promoter. similar experiments, both into WAF1/p2l gene. inhibited p53-induced 4 6 (Hep 1, HLE), there one line (HLF), enhancement evident PLC/PRF/5. transcriptional activity does occur HCC, highly cell-context-dependent. Inhibition appears to be more universal, represent mechanism which protect against