Growth control of hepatocytes, their immortalization and transformation by transforming genes of polyoma virus and of SV40 virus

Hepatocytes can be converted into permanently growing hepatocyte lines by the transforming genes of either Polyoma virus or SV40 virus. In transgenic mice (strain 202) most of the hepatocytes in the liver during late fetal development display an immortalized phenotype in culture, which is apparent immediately after placing liver cells into primary cultures. We conclude, that at the late fetal stage hepatocytes in the liver display similar properties which might be the "initiated" cell type discussed earlier which is untransformed but determined to become malignant at a later point in development. Immortalized hepatocyte lines derived from the transgenic animals display reduced growth factor requirements in culture, i.e. increased autonomy. With time in culture, cells become increasingly autonomous by further reduction of their growth requirements until the final autonomous state has been attained, i.e. growth in the absence of any growth factor or hormone. It remains to be seen whether the development of the normal liver towards HOC is accompanied by a similar increased autonomy of growth factors as observed in cells in culture. (ITA)