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Hepatic expression of SV40 small-T antigen blocks the in vivo CD95-mediated apoptosis.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2001 Jun 08; Vol. 284 (2), pp. 369-76. - Publication Year :
- 2001
-
Abstract
- 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.<br /> (Copyright 2001 Academic Press.)
- Subjects :
- Animals
Antibodies, Monoclonal pharmacology
Antigens, Polyomavirus Transforming genetics
Antigens, Polyomavirus Transforming pharmacology
Blotting, Western
Cell Transformation, Neoplastic drug effects
Cell Transformation, Neoplastic genetics
Gene Expression
In Situ Nick-End Labeling
Kidney metabolism
Liver cytology
Liver drug effects
Mice
Mice, Transgenic
Mitosis drug effects
Mitosis genetics
Mutation
NF-kappa B metabolism
Phosphorylation drug effects
Protein Structure, Tertiary genetics
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-akt
Signal Transduction drug effects
Transgenes
fas Receptor pharmacology
Antigens, Polyomavirus Transforming biosynthesis
Apoptosis drug effects
Liver metabolism
Protein Serine-Threonine Kinases
fas Receptor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 284
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 11394888
- Full Text :
- https://doi.org/10.1006/bbrc.2001.4988