Analysis of anti-tumor effect of HGF in transgenic mice

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Since we developed transgenic mice expressing HGF in liver (G.Shiota et al.Hepatology 19,962-972,1994), we have studied anti-tumor effect of HGF by using transgenic mice. First, we studied metastatic potentials of hepatocellular carcinoma (HCC) cells in chimeric mice of HGF transgenic and nude. Second, we have developed 2 kinds of double transgenic mice of HGF with TGFalpha and c-myc, and have evaluated effect of HGF on TGFalpha-or c-myc-induced hepatocarcinogenesis.1. Metastatic potential of HCC cells, such as HUH7, Hep3B and FaO cells, via portal vein was greatly suppressed in HGF/nude chimeric mice compared to nude control mice (81% vs.35%, p<0.05). 2. Double transgenic mice of TGFalpha and HGF developed HCC in 33% of mice, whereas TGFalpha mice developed HCC in 60% of mice. 3. Although c-myc mice developed adenoma and HCC in 92% and 58% of mice, HGF/c-myc double transgenic mice did 33% and 0%, respectively.