[HCV core gene transgenic mouse as a model for viral hepatocarcinogenesis]

Overwhelming lines of epidemiological evidence have indicated that chronic infection with hepatitis C virus(HCV) poses a major risk toward development of hepatocellular carcinoma(HCC). In the pathogenesis of HCC associated with HCV, it remains controversial whether these hepatitis viruses play a direct role or merely serve for an indirect role. By virtue of transgenic mouse established by us, it has become evident hat the core protein of HCV has an oncogenic potential. The findings in our studies indicate that HCV is directly involved in hepatocarcinogenesis, albeit other factors such as continued cell death and regeneration associated with chronic hepatitis may play a role, as well. Combined, our results suggest that there would be a mechanism for the development of HCC in persistent infection with hepatitis C virus that is distinct from those for the other cancers. Similar to the pathogenesis of other malignancies represented by colorectal cancer, the accumulation of a set of genetic aberrations may also be necessary for a multi-stage development of HCC. However, HCV core protein, to which an oncogenic potential is ascribed, may allow some of the multiple stages skipped in hepatocarcinogenesis. Unlike for the other cancers, therefore, infection with HCV may be capable of eliciting HCC in the absence of a complete set of genetic aberrations. Such a scenario would explain unusually high incidence and multicentric nature of HCC developing in chronic hepatitis C.