p53 transgenic mice: accelerated erythroleukemia induction by Friend virus.
Mutations in the p53 tumor-suppressor gene have been implicated in the pathogenesis of a significant proportion of human cancers and in a dominantly inherited familial cancer syndrome (Li-Fraumeni syndrome). Frequent rearrangements and point mutations have also been detected in the p53 gene in the murine erythroleukemias induced by Friend leukemia virus. We have previously reported that transgenic mice overproducing a mutated p53 protein are predisposed to the development of lung carcinomas, bone and soft-tissue sarcomas, as well as lymphoid malignancies. Here we report that p53 transgenic mice infected with the polycythemia-inducing strain of Friend virus (FV-P) progress to the late stage of erythroleukemia more rapidly than do normal mice. In addition, Friend leukemic cell lines derived from p53 transgenic mice overproduce mutant p53 protein and show a high frequency of rearrangement of the ets-related Spi-1 oncogene, as previously reported in Friend cell lines derived from non-transgenic animals. These results suggest that the same genetic changes involved in the evolution of Friend leukemia in normal mice are also required in mice with an inherited predisposition to cancer. The data also indicate that p53 transgenic mice provide an animal model in which to analyse the role that genetic and environmental factors play in influencing cancer predisposition.
Lavigueur
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Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Bernstein
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D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D005622:Friend murine leukemia virus / Q000472:pathogenicity*; D016158:Genes, p53; D015151:Immunoblotting; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000382:microbiology*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000382:microbiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D016159:Tumor Suppressor Protein p53