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-resistant phenotype, and tested several mutants of the SV40 early region for their ability to confer protection against CD95-induced apoptosis in transgenic mice. We show that resistance to apoptosis is independent of the transforming character of the mutants and demonstrate that the expression of the small-t antigen alone in transgenic mice is sufficient to confer this resistance. Our data also reveal an increased level of activated Akt kinase in these transgenic mice, and this could account for this hitherto unknown function of the SV40 small-t antigen.
Gillet
R
R
INSERM U380, Institut Cochin de Génétique Moléculaire, 22 rue Méchain, Paris, 75014, France.
Cavard
C
C
Grimber
G
G
Briand
P
P
Joulin
V
V
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects; D019076:Transgenes; D019014:fas Receptor / Q000378:metabolism* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000952:Antigens, Polyomavirus Transforming; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019014:fas Receptor; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt