Identification of a novel p53 mutation in JCV-induced mouse medulloblastoma.
Medulloblastoma, a malignant invasive tumor of the cerebellum, is one of the most common neoplasms of the nervous system in children. Utilization of the human neurotropic virus JC virus (JCV) early gene T-antigen allowed the development of a transgenic animal that models human medulloblastoma. Here we describe the characterization of two distinct populations of cells derived from the JCV-induced mouse medulloblastoma. Results from immunohistochemical and biochemical studies revealed the expression of T-antigen in some but not all tumor cells. In T-antigen-producing cells, T-antigen was found in association with wild-type p53 and pRb, two tumor suppressors that control cell growth and differentiation. In cells that lack expression of T-antigen, a novel mutant p53 with a deletion between residues 35 and 123 was detected. Morphological differences were observed between the two populations of cells, though there was no significant difference in their growth rates. However, subcutaneous transplantation of the T-antigen-positive, but not T-antigen-negative, cells resulted in the development of massive tumors in experimental animals. In light of earlier reports on the association of JCV with human medulloblastoma, the mouse cell lines described in this study may provide a valuable tool for deciphering the pathways involved in the formation and progression of medulloblastoma.
Center for Neurovirology and Cancer Biology, Laboratory of Brain Tumor Biology, College of Science and Technology, Temple University, 1900 North 12th Street, 015-96, Biology Life Sciences Building, Room 203, Philadelphia, Pennsylvania 19122, USA.
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B
Krynska
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L
Del Valle
J
J
Gordon
J
J
Otte
S
S
Croul
K
K
Khalili
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism*; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D002531:Cerebellum / Q000166:cytology; D006801:Humans; D007577:JC Virus / Q000502:physiology*; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009154:Mutation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D016159:Tumor Suppressor Protein p53