Expression of integrated hepatitis B virus X variants in human hepatocellular carcinomas and its significance

Hepatitis B virus X protein (HBX) has been implicated in the transactivatio n of diverse cellular genes and possibly also the pathogenesis of human hep atocellular carcinoma (HCC). We report the characterization of HEX variants from HBV-related human hepatocellular carcinoma (HCC). These HEX variants were integrated into the host chromosomes and also expressed in the HCC tis sues. In addition, we report a novel in vitro HEX activity assay based on c olor changes that were indicative of the beta-galactosidase enzyme activity . Conducted in wheat germ lysates, the transactivating function of either w ild type or mutant HEX protein was measured through their interaction with the Early Growth Response factor 1 (Egr-1) that controls the beta-galactosi dase gene. Further analysis of these HEX deletion mutants using this assay may shed new insights on the significance of various mutations occurring in HCC-associated HEX. (C) 2000 Academic Press.