Mouse model for lung tumorigenesis through Cre/lox controlled sporadic activation of the K-Ras oncogene

The onset of human lung cancer occurs through sequential mutations in oncog enes and tumor suppressor genes. Mutations in K-Ras play a prominent role i n human non-small cell lung cancer. We have developed a mouse lung tumor mo del in which K-Ras can be sporadically activated through Cre-lox mediated s omatic recombination. Adenoviral mediated delivery of Cre recombinase in lu ng epithelial cells gave rise to rapid onset of tumorigenesis, yielding pul monary adenocarcinomas with 100% incidence after a short latency. The lung tumor lesions shared many features with human non-small cell lung cancer. O ur data show that sporadic expression of the K-Ras oncogene is sufficient t o elicit lung tumorigenesis. Therefore this model has many advantages over conventional transgenic models used thus far.