THE MECHANISMS OF CELL TRANSFORMATION INDUCED BY HEPATITIS CVIRUS
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||KYOTO UNIVERSITY|
HIJIKATA Makoto KYOTO UNIVERSITY THE INSTITUTE FOR VIRUS RESEARCH,DEPARTMENT OF VIRAL ONCOLOGY,ASSOCIATE PROFESSOR, ウイルス研究所, 助教授 (90202275)
|Project Period (FY)
1997 – 1998
Completed(Fiscal Year 1998)
|Budget Amount *help
¥2,700,000 (Direct Cost : ¥2,700,000)
Fiscal Year 1998 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1997 : ¥1,800,000 (Direct Cost : ¥1,800,000)
|Keywords||hepatitis C virus / hepatitis / hepatocellular carcinoma / persistent infection / apoptosis / NF-kappaB / transfomation / polypyrimidine tract binding protein|
To reveal the molecular mechanisms of hepatitis and hepatocellular carcinoma closely related with the infection of hepatitis C virus (HCV), we investigated the changes of the gene expression in the HCV protein producing cultured cells originated from hepatocytes and analyzed the cellular factor interacting with HCV genome and its gene products. The results are followed ;
1. We found a cellular factor interacting with the terminal fragment of HCV genome in the cell lysate by U.V.cross link method. We showed that the factor was the polypyrimidine tract binding protein.
2. We obtained HepG2 cells producing a HCV proteins after specific concentration of the transiently plasmid transfected cells. The mRNA samples from the cells with and without HCV protein production were used for dot blothybridization experiment using more than 500 fragments of the cellular genes as targets. However no drastic change of the expression was found.
3. We found that the concentrated HepG2 cells producing HCV prot
eins became resistant against Fas and tumor necrosis factor (TNF)-alpha mediated apoptosis This function was appeared to be responsible to the core protein among a HCV proteins.
4. We revealed that the core protein functioned as an anti-apoptotic factor by synergistic enhancement of NF-kappaB activity induced by apoptotic signals, anti Fas antibody and TNF-alpha in certain cells. We also found that there was a NF-kappaB-independent anti-apoptotic pathway by HCV core protein.
5. We showed that the core protein have a potential to transform a certain cells cooperatively with an oncogenic protein, Ras.
6. The core protein was revealed to have a potential to activate the cell proliferation through the activation of MAP kinase cascade. We consider that the anti-apoptotic effect and transforming potential of the core protein may contribute to the persistent infection of HCV and cause of hepatocellular carcinoma.
Further analysis of molecular mechanisms of these functions of the core protein is underway. Less
Research Output (18results)