| Project/Area Number |
07670628
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kanazawa Meidcal University |
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Principal Investigator |
HASUMURA Yasushi Kanazawa Medical University, Medical Research Institute, Professor, 総合医学研究所, 教授 (40019956)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEGAMI Tsutomu Kanazawa Medical University, Medical Research Institute, Associate Professor, 総合医学研究所, 助教授 (10113490)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | hepatitis C virus / virus nonstructural protein NS3 / carcinogenesis / cell transformation |
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| Research Abstract |
The association of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) infection has been suggested. However, its mechanism is unknown. Because the organization of HCV resembles that of members of the family Flaviviridae, a biological function of the HCV nonstructural protein NS3 may play a role. To test this, either human- or mouse-associated cells were transfected with an expression vector containing cDNA for the 5'-or 3'-half sequence of the HCV genome segment encoding NS3 (pRcHCNS3-5' and pRcHCNS3-3', respectively).
1. When Hep G2 cells or IMR32 cells were transfected with the vectors, HCV-specific DNA was detected only in the cells transfected with pRcHCNS3-5'.
2. NIH 3T3 cells were transfected and cell growth were determined. Only cells transfected with pRcHCNS3-5' rapidly proliferated and indeed, showed the colony formations.
3. NIH 3T3 cells transfected with pRcHCNS3-5' were inoculated subcutaneously in the flank of nude mice. After 2 weeks of the inoculation, subcutaneous tumors were found 2 of 10 inoculated mice. In particular, all mice developed the tumor, which was defined microscopically as fibrosarcoma.
4. The HCV-specific DNA fragment was able to be amplified in cells isolated from the tumors.
These results suggest that 5' region of HCV-NS3 is involved in cell transformation. Further studies are needed to see whether this tumorigenic capability associated with the 5' region of HCV-NS3 plays a significant role for the carcinogenesis of the HCV-infected liver.
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