Hepatitis C virus F protein up-regulates c-myc and down-regulates p53 in human hepatoma HepG2 cells

Intervirology. 2007;50(5):341-6. doi: 10.1159/000107271. Epub 2007 Aug 15.

Abstract

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Gene Expression Regulation*
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Humans
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Viral Core Proteins / genetics
  • Viral Core Proteins / physiology*

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • Viral Core Proteins
  • hepatitis C protein F, Hepatitis C virus
  • nucleocapsid protein, Hepatitis C virus