[The role of hepatitis B virus X gene and p53 on hepatocellular carcinoma cell growth].
OBJECTIVE
To explore the effects of hepatitis B virus X gene and p53 on hepatocellular growth.


METHODS
Two kinds of plasmids containing sense and antisense human wild p53 gene respectively were constructed. SMMU-7721 cells were transfected with HBx, sense-wtp53 antisense-wtp53 separately or cotransfected with either HBx and sense-wtp53 or HBx and antisense-wtp53. Flow cytometry was adopted to measure the apoptosis rates and the effects of HBx on cell cycle progression. The activity of p21(Waf1) promoter-luciferase construct was detected. Growth curves for SMMU-7721 stably transfected with pcDNA3 and pcDNA3HBx were analyzed.


RESULTS
After doxorubicin administration, HBx was noticed able to initiate apoptosis of the liver cells. The apoptosis rate was 5.32% in the pcDNA3 transfected and 12.66% in the pcDNA3HBx transfected groups respectively. HBx could also abrogate p53-mediated apoptosis. The apoptosis rate in groups transfected with pcDNA3, pcDNA3wtp53 and pcDNA3HBx + pcDNA3wtp53 was 5.32%, 11.72% and 4.67% respectively. In compared with the normal group, the number of cells in transiently HBx-expressed group and HBx-transfected group decreased 4.79% and 10.25% respectively. HBx inhibited the activity of p21(Waf1) promoter-luciferase constructed (P < 0.05) and promoted cell growth. The growth rate of HBx expression cells was faster.


CONCLUSIONS
Under DNA damage, HBx reduced expression of p21(Waf1) by repressing the activity of p53 protein, followed by disturbing the regulation of G(0)-G(1) cell cycle checkpoint, and promoted the growth rate of hepatoma cells.
Lin
Jing
J
Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Zhu
Ming-hua
MH
Zhu
Shi
S
Qu
Jian-hui
JH
Li
Fang-mei
FM
Ni
Can-rong
CR
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology; D002455:Cell Division; D045744:Cell Line, Tumor; D016158:Genes, p53; D006511:Hepatitis B Antigens / Q000096:biosynthesis / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000821:virology; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins
D006511:Hepatitis B Antigens; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein