Analysis of a mutant p53 protein arising in a medulloblastoma from a mouse transgenic for the JC virus early region.

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
• Journal: Anticancer research (Anticancer Res) 2006 Nov-Dec Vol. 26 Issue 6B Pg. 4079-92 ISSN: 0250-7005 [Print] Greece
• PMID: 17201119 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

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)