Somatic activation of the K-ras oncogene causes early onset lung cancer in mice.

Nature 2001 Apr;410(6832):1111-6

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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.

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http://www.nature.com/articles/35074129
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April 2001
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References

(Supplied by CrossRef)

JL Bos et al.
Cancer Res. 1989

R Khosravi-Far et al.
Cancer Met. Rev. 1994

JL Bos et al.
Nature 1987

NE Mills et al.
Cancer Res. 1995

NS Pellegata et al.
Cancer Res. 1994

B Vogelstein et al.
N. Engl. J. Med. 1988

JM Adams et al.
Science 1991

P Hasty et al.
Nature 1991

L Johnson et al.
Genes Dev. 1997

PK Seperack et al.
Proc. Natl Acad. Sci. USA 1988

EV Thrane et al.
Exp. Lung Res. 1997

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