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.


CONCLUSIONS
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.
Ye
Lihong
L
Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, PR China.
Dong
Nan
N
Wang
Qi
Q
Xu
Zhili
Z
Cai
Na
N
Wang
Honghui
H
Zhang
Xiaodong
X
D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000032:analysis; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
D020543:Proteome; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein