Carcinogenesis, Vol 18, 1423-1426, Copyright © 1997 by Oxford University Press
M Shafarenko, J Mahler, C Cochran, A Kisielewski, E Golding, R Wiseman and T Goodrow
Mutated p53 genes are capable of complementing activated ras genes in the
transformation of primary rat embryo fibroblasts in vitro. Mutations in
both genes have also been found in several human cancers, including lung
carcinomas. We generated transgenic mice containing a p53 construct with a
missense mutation in exon 5 (ala135val) to study the role of p53 mutations
in lung tumorigenesis, and to facilitate identification of other genetic
events that might complement p53 mutations in mouse lung carcinogenesis.
The p53 transgenic lines exhibited a higher frequency of lethal lung tumors
than the parental FVB/N strain. We examined the spontaneously-arising lung
carcinomas from mice expressing the mutated p53 transgene for K-ras
mutations using single-stranded conformation polymorphism (SSCP) and/or
direct sequencing approaches. Fifteen of 29 (52%) carcinomas contained
mutations in the K-ras oncogene. Six of 15 of the K-ras mutations were in
codon 61 and 9/15 were in codon 12. Subsequent analysis of spontaneous lung
carcinomas from mice of the FVB/N parental strain showed that 9/12 (75%)
carcinomas examined contained K-ras mutations. Two of these were in codon
12, one in codon 13, and 6 were in codon 61. These results demonstrate that
the frequency of ras mutations does not differ between the p53 FVB/N
transgenic mice and their parental FVB/N strain but suggest that a high
frequency of mutations K-ras can be correlated with lung tumorigenesis in
both groups of mice.
ARTICLES
Similar incidence of K-ras mutations in lung carcinomas of FVB/N mice and FVB/N mice carrying a mutant p53 transgene
Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
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