| Abstract | BACKGROUND: JC virus (JCV) is a polyomavirus that causes progressive multifocal leukoencephalopathy (PML) in humans and is highly oncogenic in experimental animals. Transgenic mice with JCV T-antigen develop cerebellar tumors, which resemble human medulloblastomas, containing two distinct cell subpopulations, T-antigen positive and negative. In T-negative clones, a novel mutant p53 was detected (p53(mt)). MATERIALS AND METHODS: We have compared p53(mt) to wild-type p53 (p53wt) in p53-null cells. RESULTS: p53(mt) had lost the transcriptional transactivation activity of p53(wt), and unlike p53(wt), partially localized to the cytoplasm. Unlike mutant p53 from many human cancers, p53(mt) did not show a gain of function or a dominant negative phenotype. Adenovirus expressing p53(wt) but not p53(mt) inhibited cell growth and induced apoptosis of p53-null cells. CONCLUSION: During the course of tumor evolution of the JCV T-antigen mouse medulloblastoma, a mutation occurred that inactivated p53 allowing tumor progression even in the absence of continued T-antigen expression. |
| Authors | Martyn K White, Anna Skowronska, Jennifer Gordon, Luis Del Valle, Satish L Deshmane, Antonio Giordano, Kamel Khalili
(Affiliation: Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA 19122, USA. martyn.white at temple.edu)
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| Journal | Anticancer research
(Anticancer Res)
2006 Nov-Dec
Vol. 26
Issue 6B
Pg. 4079-92
ISSN: 0250-7005 Greece |
| PMID | 17201119
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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| Chemical References |
- Tumor Suppressor Protein p53
|
| Topics |
- Animals
- Brain Neoplasms
(metabolism, virology)
- Cell Line, Tumor
- Flow Cytometry
- Humans
- Immunohistochemistry
- JC Virus
(genetics)
- Medulloblastoma
(metabolism, virology)
- Mice
- Mice, Transgenic
- Mutation
- Tumor Suppressor Protein p53
(genetics, metabolism)
|
