Oncogenic potential of hepatitis B virus.
The function of the X gene was clarified by examination of the transient production of hepatitis B virus (HBV) particles by transfected recombinant HBV DNA (pHBV-3 DNA) and its frameshift mutant (delta X) of the X open reading frame into hepatocellular carcinoma HuH-7 and HepG2 cells. No reduction of viral mRNAs was observed in the HuH-7 cells by the delta X mutant, whereas mRNAs underwent marked reduction in HepG2 cells. No reduction in core particle production was observed in HuH-7 cells, but in HepG2 cells reduction was considerable. To clarify the significance of the delta X mutation in the trans-acting function of the X gene in hepatoma cells, the chloramphenicol acetyl/transferase (CAT) assay was conducted. Transfection of plasmid pHBV-3 into HepG2 cells increased CAT activity of pSV2-CAT, while the delta X mutation clearly showed no stimulation of activity. On the other hand, in the HuH-7 cells, pHBV-3 exhibited no such stimulation. The trans-acting function of the X gene product in two different hepatoma cells was clearly shown to differ. Furthermore, transfection of X gene expression plasmid pKSV-HBx into mouse NIH3T3 cells increased the CAT activity of pSV2-CAT. Trans-activation was still detectable even following deletion of enhancer sequences in the pSV2CAT. The oncogenic potential of HBV is discussed with special attention to the X gene product, which may be able to activate a cellular transcription factor at the viral and cellular promotor sequences in the cells.
Koike
K
K
Department of Gene Research, Cancer Institute, Tokyo, Japan.
Shirakata
Y
Y
Yaginuma
K
K
Arii
M
M
Takada
S
S
Nakamura
I
I
Hayashi
Y
Y
Kawada
M
M
Kobayashi
M
M
D000818:Animals; D004279:DNA, Viral / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009857:Oncogenes; D010957:Plasmids; D015534:Trans-Activators; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D004279:DNA, Viral; D015534:Trans-Activators