Hepatic expression of SV40 small-t antigen blocks the in vivo CD95-Mediated apoptosis

We have previously demonstrated that CD95-mediated apoptosis of hepatocytes is blocked in a murine model of hepatocarcinogenesis due to the expression of SV40 early sequences encoding the large-T and small-t antigens. In this study, we set out to pinpoint the sequences involved in this apoptosis-res istant phenotype, and tested several mutants of the SV40 early region for t heir ability to confer protection against CD95-induced apoptosis in transge nic mice. We show that resistance to apoptosis is independent of the transf orming character of the mutants and demonstrate that the expression of the small-t antigen alone in transgenic mice is sufficient to confer this resis tance. Our data also reveal an increased level of activated Akt kinase in t hese transgenic mice, and this could account for this hitherto unknown func tion of the SV40 small-t antigen. (C) 2001 Academic Press.