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

Abstract

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.

• Authors: Lihong Ye, Nan Dong, Qi Wang, Zhili Xu, Na Cai, Honghui Wang, Xiaodong Zhang
• Journal: Intervirology (Intervirology) Vol. 51 Issue 1 Pg. 50-8 ( 2008) ISSN: 1423-0100 [Electronic] Switzerland
• PMID: 18334850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2008 S. Karger AG, Basel.

Chemical References

• Proteome
• Trans-Activators
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein

Topics

• Apoptosis
• Blotting, Western
• Cell Line, Tumor
• Cell Transformation, Viral
• Gene Expression Profiling
• Gene Expression Regulation
• Gene Silencing
• Hepatitis B virus (physiology)
• Hepatocytes (virology)
• Humans
• Oligonucleotide Array Sequence Analysis
• Proteome (analysis)
• Trans-Activators (antagonists & inhibitors, physiology)
• Viral Regulatory and Accessory Proteins