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 (p53(mt)).


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.


CONCLUSIONS
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.
White
Martyn K
MK
Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA 19122, USA. martyn.white@temple.edu
Skowronska
Anna
A
Gordon
Jennifer
J
Del Valle
Luis
L
Deshmane
Satish L
SL
Giordano
Antonio
A
Khalili
Kamel
K
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000821:virology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000235:genetics*; D008527:Medulloblastoma / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53