Progressive changes in hepatoma cells stably transfected with hepatitis B virus X gene.

OBJECTIVE

The aim of this study is to investigate the molecular mechanism of hepatocellular carcinoma (HCC) development induced by hepatitis B virus X protein (HBx).

METHODS

We previously established a H7402-X cell line that constitutively expresses HBx protein. In the present study, H7402-X gene expression profiles and proteins were examined using cDNA microarrays and Western blot analysis. Apoptosis was induced by adriamycin in H7402-X cells. The transcriptional activities of NF-kappaB and AP-1 were examined using a luciferase reporter gene.

RESULTS

The DNA expression profiles identified candidate genes showing aberrant expression in cells overexpressing HBx. Western blot analysis showed that cyclin D, cyclin E, survivin, Bcl-2, and PCNA were up-regulated, whereas p27 was down-regulated in H7402-X cells. Treatment with RNAi targeting HBx mRNA led to the down-regulation of these genes. H7402-X cells were resistant to adriamycin-induced apoptosis. Luciferase reporter gene analysis revealed that HBx induces the transcriptional activities of NF-kappaB and AP-1.

CONCLUSION

Our data provide additional insight into cellular targets of HBx, which allows a better understanding of HBx function and the progressive changes during HBx-mediated hepatocarcinogenesis.