Conditional expression of mutated K-ras accelerates intestinal tumorigenesis in Msh2-deficient mice

F Luo, D G Brooks, H Ye, R Hamoudi, G Poulogiannis, C E Patek, D J Winton, M J Arends

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

K-ras mutation occurs in 40-50% of human colorectal adenomas and carcinomas, but its contribution to intestinal tumorigenesis in vivo is unclear. We developed K-ras(V12) transgenic mice that were crossed with Ah-Cre mice to generate K-ras(V12)/Cre mice, which showed beta-naphthoflavone-induction of Cre-mediated LoxP recombination that activated intestinal expression of K-ras(V12) 4A and 4B transcripts and proteins. Only very occasional intestinal adenomas were observed in beta-naphthoflavone-treated K-ras(V12)/Cre mice aged up to 2 years, suggesting that mutated K-ras expression alone does not significantly initiate intestinal tumourigenesis. To investigate the effects of mutated K-ras on DNA mismatch repair (MMR)-deficient intestinal tumour formation, these mice were crossed with Msh2(-/-) mice to generate K-ras(V12)/Cre/Msh2(-/-) offspring. After beta-naphthoflavone treatment, K-ras(V12)/Cre/Msh2(-/-) mice showed reduced average lifespan of 17.3+/-5.0 weeks from 26.9+/-6.8 (control Msh2(-/-) mice) (P
Original languageEnglish
Pages (from-to)4415-27
Number of pages13
Issue number30
Publication statusPublished - 28 Jun 2007

Keywords / Materials (for Non-textual outputs)

  • Animals
  • DNA Mismatch Repair
  • Genes, ras
  • Integrases
  • Intestinal Neoplasms
  • MAP Kinase Signaling System
  • Mice
  • Mice, Transgenic
  • MutS Homolog 2 Protein
  • Mutation
  • Proto-Oncogene Proteins c-akt
  • Thymoma
  • Thymus Neoplasms


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