Cancer Cell
Volume 4, Issue 2, August 2003, Pages 111-120
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Article
Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context

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Abstract

We have targeted a K-ras allele in mouse embryonic stem (ES) cells to express a K-RasV12 oncoprotein along with a marker protein (β-geo) from a single bicistronic transcript. Expression of this oncogenic allele requires removal of a knocked in STOP transcriptional cassette by Cre recombinase. Primary mouse embryonic fibroblasts expressing this K-rasV12 allele do not undergo proliferative senescence and proliferate as immortal cells. In mice, expression of K-rasV12 throughout the body fails to induce unscheduled proliferation or other growth abnormalities for up to eight months. Only a percentage of K-rasV12-expressing lung bronchiolo-alveolar cells undergo malignant transformation leading to the formation of multiple adenomas and adenocarcinomas. These results indicate that neoplastic growth induced by an endogenous K-ras oncogene depends upon cellular context.

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Present Address: Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain