Activation of protooncogenes in mouse lung tumors. Exp Lung Res 1991;17(2):389-400
Date
03/01/1991Pubmed ID
2050038DOI
10.3109/01902149109064426Scopus ID
2-s2.0-0026034579 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
The detection of activated protooncogenes in mouse lung tumors has led to a major advance in our understanding of carcinogenesis of the lung at the molecular level. A high frequency of activated K-ras protooncogenes has been detected in tetranitromethane (TNM)- and 1,3-butadiene-induced lung tumors in B6C3F1 mice. In the past several years, we have pursued protooncogene activation in spontaneous and chemically induced tumors of strain A mice. The strain A mouse has a high incidence of spontaneous lung tumors and is susceptible to tumor induction by chemical carcinogens. We have detected and characterized the activated protooncogenes in the DNA of both spontaneously occurring and chemically induced lung tumors of strain A mice. Activated K-ras genes were detected using the NIH/3T3 transfection assay, and the activating mutations were identified by utilizing the polymerase chain reaction (PCR) and direct sequence analysis. A strong selectivity of mutations in the K-ras genes were observed in chemically induced lung tumors, as compared to spontaneous tumors, indicating that the carcinogens directly induced point mutations in the K-ras protooncogene. These findings suggest that the strain A mouse lung tumor model appears to be a very sensitive system to identify the mechanism by which chemical carcinogens activate the K-ras gene in lung tissue in vivo.
Author List
You M, Wang Y, Lineen A, Stoner GD, You LA, Maronpot RR, Anderson MWMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Southern
DNA, Neoplasm
Gene Amplification
Gene Expression Regulation, Neoplastic
Genes, ras
Lung Neoplasms
Mice
Mice, Inbred A
Mutation
Proto-Oncogenes
Transfection