A mouse model for tumor progression of lung cancer in ras and p53 transgenic mice. Oncogene 2006 Feb 23;25(8):1277-80
Date
10/26/2005Pubmed ID
16247444DOI
10.1038/sj.onc.1209182Scopus ID
2-s2.0-33644504228 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Although ras and p53 are the most commonly found oncogene and tumor suppressor gene, respectively, in human cancers, their collective roles in tumor progression have yet to be defined in animal models. Here, we demonstrated the synergistic effect between ras and p53 in promoting tumor progression during lung tumorigenesis using bitransgenic mice. Mice with a heterozygous knockout of K-ras (K-ras(wt/ko)) were mated to p53 transgenic mice (p53(val135/wt)) in lung tumorigenesis (K-ras(wt/ko) x p53(val135/wt)). F(1) mice exhibited a significant increase in lung tumor load (tumor multiplicity x tumor volume) when compared to those seen in either K-ras(wt/ko) mice or p53(val135/wt) mice alone. Furthermore, over 50% of the lung tumors were lung adenocarcinomas in bitransgenic mice compared to only 3% in wild-type mice. Alterations of ras and p53 appear to promote the development of lung adenocarcinomas. These results provide the in vivo experimental evidence of synergistic interactions of ras and p53 in lung tumor progression.
Author List
Wang Y, Zhang Z, Lubet RA, You MMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAnimals
Cocarcinogenesis
Disease Models, Animal
Disease Progression
Genes, ras
Heterozygote
Humans
Lung Neoplasms
Mice
Mice, Knockout
Mice, Transgenic
Tumor Suppressor Protein p53
Urethane
