Tumorigenesis in transgenic mice by a nuclear transport-defective SV40 large T-antigen gene |
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| Authors: | C A Pinkert R L Brinster R D Palmiter C Wong J S Butel |
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| Affiliation: | 1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;2. Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;3. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;4. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;5. Goizueta Alzheimer''s Disease Center, Emory University School of Medicine, Atlanta, GA, USA;6. Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA;7. Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA;8. Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA;9. Veterans Affairs Atlanta Health Care System, Decatur, GA, USA;10. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA;11. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA;12. Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Street, Bronx, NY, USA;13. Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center, Street, Bronx, NY, USA;1. Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;2. Department of Oncology, University of Cambridge, Cambridge, UK |
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| Abstract: | The SV40(cT) mutant encodes a large tumor antigen (cT-ag) that is defective for transport from the cell cytoplasm into the nucleus. This mutant is able to transform established cell lines at near wild-type virus efficiencies, but has a markedly decreased ability to transform primary cells and to induce tumors in newborn hamsters (R. E. Lanford, C. Wong, and J. S. Butel, 1985, Mol. Cell. Biol. 5, 1043-1050). To explore the biology of transport-defective T-ag in vivo, transgenic mice carrying the cT-ag gene were produced. Five of eight founder animals died early in life of choroid plexus tumors (mean age +/- SE, 52 +/- 11.0 days); renal and thymic lesions were also observed. Mice of an SV40(cT) transgenic line regularly succumb to brain tumors (mean age, 81 +/- 1.2 days). SV40 T-ag is expressed in the tumor cells and is retained in the cytoplasm. The observation that SV40(cT) is equivalent to wild-type virus at tumor induction in transgenic mice emphasizes the probable importance of extranuclear forms of SV40 T-ag in brain tumor formation. This study also indicates that in vitro cell transformation assays may not always be accurate reflections of the oncogenic potential of a transforming gene in vivo, because of the different cell types involved. |
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