Clinical evidence suggests that hepatitis C virus (HCV) is etiological
ly involved in hepatic cancer and liver cirrhosis. To investigate whet
her the HCV nonstructural protein NS3 has oncogenic activity, NM 3T3 c
ells were transfected with an expression vector containing cDNA for th
e 5'- or 3'-half sequence of the HCV genome segment encoding NS3. Only
cells transfected with the 5'-half cDNA rapidly proliferated, lost co
ntact inhibition, grew anchorage independently in soft agar, and forme
d tumors in nude mice. PCR analysis confirmed the presence of the 5'-h
alf DNA in the transfectants These results suggest that the 5' region
of the HCV genome segment encoding NS3 is involved in cell transformat
ion.