Hepatitis B virus X gene differentially modulates cell cycle progression and apoptotic protein expression in hepatocyte versus hepatoma cell lines.

The hepatitis B virus (HBV) X gene, which encodes the hepatitis B virus x protein (HBx), is essential for viral infection and genome replication, virus-associated liver disease, and development of hepatocellular carcinoma. However, the exact role(s) of HBx remain controversial. In this study, we focus on studying the role of HBx in the regulation of cell cycle and apoptosis in normal liver and hepatoma cell lines. We established the Huh7-X and Chang-X cell lines that constitutively express HBx. There were differences between the two cell lines in terms of cell cycle regulation and expression of p27 and transforming growth factor-β. Expression of HBx proteins dramatically increases expression of Bcl-2 and reduces levels of cleaved PARP protein in Chang-X cells, and it inhibits apoptosis under unfavourable conditions, such as serum starvation, in both cell lines. Our findings provide clues about the intracellular roles of HBx and demonstrate that expression of this protein is important for multiple cellular processes, that is, cell cycle progression and apoptosis, in hepatoma cells and normal liver cell lines.