Hepatitis C virus F protein up-regulates c-myc and down-regulates p53 in human hepatoma HepG2 cells.
OBJECTIVE
Hepatitis C virus (HCV) F protein is a newly identified protein encoded by an alternative open reading frame that +1 overlaps core-encoding gene. It has been found that regulation of c-myc and p53 genes by HCV core protein is involved in liver cancer genesis. We wondered whether HCV F protein exerts similar or adverse regulatory effects on the transcription of c-myc and p53 genes.


METHODS
HCV F gene-containing, plasmid pcDNA3.1-F and HCV core gene-containing pcDNA3.1-C were constructed and transiently transfected into HepG(2) cells. Real-time quantitative PCR or Western blotting was used to determine the changes at transcription or translation levels of c-myc and p53 genes.


RESULTS
The transcription level of c-myc was much higher in pcDNA3.1-F transfected cells than those without plasmid transfected. Whereas the level of p53 transcription in pcDNA3.1-F transfected cells was lower than those in the parental cells. Moreover, levels of c-myc expression were up-regulated and those of p53 expression were down-regulated by HCV F protein.


CONCLUSIONS
HCV F protein is of regulatory properties in cellular oncogene c-myc and anti-oncogene p53, which may be implicated in the formation of hepatocellular carcinoma.
Wu
Wen-bin
WB
Department of Microbiology, State Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, PR China.
Shao
Sheng-wen
SW
Zhao
Lan-juan
LJ
Luan
Jie
J
Cao
Jie
J
Gao
Jun
J
Zhu
Shi-ying
SY
Qi
Zhong-tian
ZT
D015153:Blotting, Western; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014758:Viral Core Proteins / Q000235:genetics / Q000502:physiology*
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus; C069130:nucleocapsid protein, Hepatitis C virus