Somatic activation of the K-ras oncogene causes early onset lung cancer in mice.
Document Type
Article
Publication Date
2001
Keywords
Animal, Cell-Line, Disease-Models-Animal, Gene-Expression-Regulation, Gene-Targeting, Genes-p53, Genes-ras, Human, Lung-Neoplasms, Lymphoma, Mice, Mice-Inbred-C57BL, Mutation, Papilloma, Recombination-Genetic, Skin-Neoplasms, SUPPORT-NON-U-S-GOVT, Thymus-Neoplasms
First Page
1111
Last Page
1116
JAX Source
Nature 2001 Apr; 410(6832):1111-6.
Abstract
About 30% of human tumours carry ras gene mutations. Of the three genes in this family (composed of K-ras, N-ras and H-ras), K-ras is the most frequently mutated member in human tumours, including adenocarcinomas of the pancreas ( approximately 70-90% incidence), colon (approximately 50%) and lung ( approximately 25-50%). To construct mouse tumour models involving K-ras, we used a new gene targeting procedure to create mouse strains carrying oncogenic alleles of K-ras that can be activated only on a spontaneous recombination event in the whole animal. Here we show that mice carrying these mutations were highly predisposed to a range of tumour types, predominantly early onset lung cancer. This model was further characterized by examining the effects of germline mutations in the tumour suppressor gene p53, which is known to be mutated along with K-ras in human tumours. This approach has several advantages over traditional transgenic strategies, including that it more closely recapitulates spontaneous oncogene activation as seen in human cancers.
Recommended Citation
Johnson L,
Mercer K,
Greenbaum D,
Bronson RT,
Crowley D,
Tuveson DA,
Jacks T.
Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature 2001 Apr; 410(6832):1111-6.