Transactivation of the human MDRI gene by hepatitis B virus X gene product

Background/Aims: Persistent hepatitis B virus (HBV) infection may cause hep atocellular carcinoma. Patients with hepatocellular carcinoma rape characte rized by nonresponsiveness to chernotherapeut-fe agents, While many studies have been devoted to understanding the hepatocarcinogenesis mechanism of H BV, the possible relationship between HBV and the drug sensitivity phenotyp e of cancer cells has rarely Been addressed. The hepatitis B; virus X gene encodes transcription transactivator which has been suggested to be a poten tial factor in viral hepatocarcinogenesis. The role of HBV pX in mediating the drag resistance phenotype of hepatoma cell lines was examined in this s tudy. Methods: Standard transfection and chloramphenicol acetyltransferase assay were utilized to examine the effect of HBV pX transactivator on a reporter gene under the control of the human multidrug resistance (MDR) 1 upstream r egulatory elements. Selected Hep G2 clones with or without HBV pX expressio n were tested for their sensitivity towards various anti-cancer agents by u tilization of MTT assay. Results: The expression of HBV pX in both Hep G2 (p53+) and Hep 3B (p53-) c ells resulted in transactivation of the reporter gene under control of the human MDR1 upstream regulatory elements. Northern blot analysis indicated t hat expression of the endogenous MDR1 gene was also elevated in Hep G2 clon es with HBV pX expression. Decreased drug sensitivity towards adriamycin, v inblastine, and VP-16 was observed in Hep G2 clones with HBV pX expression. Conclusions: HBV pX can transactivate the MDR1 gene. Drug sensitivity was a ltered in Hep G2 cells with HBV pX expression.