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

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 (p53mt). Materials and Methods: We have compared p53mt to wild-type p53 (p53wt) in p53-null cells. Results: p53mt had lost the transcriptional transactivation activity of p53wt, and unlike p53wt, partially localized to the cytoplasm. Unlike mutant p53 from many human cancers, p53mt did not show a gain of function or a dominant negative phenotype. Adenovirus expressing p53wt but not p53mt 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.