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

doi:10.1038/sj.onc.1210231

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

Deanery of Molecular, Genetic and Population Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English
Pages (from-to)	4415-27
Number of pages	13
Journal	Oncogene
Volume	26
Issue number	30
DOIs	https://doi.org/10.1038/sj.onc.1210231
Publication status	Published - 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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10.1038/sj.onc.1210231

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title = "Conditional expression of mutated K-ras accelerates intestinal tumorigenesis in Msh2-deficient mice",

abstract = "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",

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author = "F Luo and Brooks, {D G} and H Ye and R Hamoudi and G Poulogiannis and Patek, {C E} and Winton, {D J} and Arends, {M J}",

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doi = "10.1038/sj.onc.1210231",

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T1 - Conditional expression of mutated K-ras accelerates intestinal tumorigenesis in Msh2-deficient mice

AU - Luo, F

AU - Brooks, D G

AU - Ye, H

AU - Hamoudi, R

AU - Poulogiannis, G

AU - Patek, C E

AU - Winton, D J

AU - Arends, M J

PY - 2007/6/28

Y1 - 2007/6/28

N2 - 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

AB - 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

KW - Animals

KW - DNA Mismatch Repair

KW - Genes, ras

KW - Integrases

KW - Intestinal Neoplasms

KW - MAP Kinase Signaling System

KW - Mice

KW - Mice, Transgenic

KW - MutS Homolog 2 Protein

KW - Mutation

KW - Proto-Oncogene Proteins c-akt

KW - Thymoma

KW - Thymus Neoplasms

U2 - 10.1038/sj.onc.1210231

DO - 10.1038/sj.onc.1210231

M3 - Article

C2 - 17297472

SN - 0950-9232

VL - 26

SP - 4415

EP - 4427

JO - Oncogene

JF - Oncogene

IS - 30

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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