Hepatitis B virus X protein mutants exhibit distinct biological activities in hepatoma Huh7 cells.
The role of the hepatitis B virus X protein (HBx) in hepatocarcinogenesis remains controversial. To investigate the biological impact of hepatitis B virus x gene (HBx) mutation on hepatoma cells, plasmids expressing the full-length HBx or HBx deletion mutants were constructed. The biological activities in these transfectants were analyzed by a series of assays. Results showed that HBx3'-20 and HBx3'-40 amino acid deletion mutants exhibited an increase in cellular proliferation, focus formation, tumorigenicity, and invasive growth and metastasis through promotion of the cell cycle from G0/G1 to the S phase, when compared with the full-length HBx. In contrast, HBx3'-30 amino acid deletion mutant repressed cell proliferation by blocking in G1 phase. The expression of P53, p21(WAF1), p14(ARF), and MDM2 proteins was regulated by expression of HBx mutants. In conclusions, HBx variants showed different effects and functions on cell proliferation and invasion by regulation of the cell cycle progression and its associated proteins expression.
Liu
Xiaohong
X
Department of Pathology, Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433, PR China.
Zhang
Shuhui
S
Lin
Jing
J
Zhang
Shunmin
S
Feitelson
Mark A
MA
Gao
Hengjun
H
Zhu
Minghua
M
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002453:Cell Cycle; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009361:Neoplasm Invasiveness; D010957:Plasmids; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D017384:Sequence Deletion; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015534:Trans-Activators; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2