Colon-specific tumorigenesis in mice driven by Cre-mediated inactivation of Apc and activation of mutant Kras

Alexander J. Byun, Kenneth E. Hung, James C. Fleet, Roderick T. Bronson, Joel B. Mason, Paloma E. Garcia, Jimmy W. Crott

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Several genetically engineered mouse (GEM) models of colorectal cancer have been developed and are a mainstay in our efforts to identify means of preventing and treating this disease. Many of these models involve a germline disruption of the adenomatous polyposis coli (Apc) tumor suppressor gene and share the limitation that the great preponderance of tumors appear in the small rather than large intestine. In recent years efforts have been made to increase the similarity of these models to human sporadic colorectal cancer by disrupting Apc in a tissue-specific fashion using the Cre-Lox system so that the genetic aberrations are confined to the colonic epithelium. These models have shown great promise but reproducible and high penetrance colon-specific tumorigenesis has not yet been achieved without invasive techniques to introduce the Cre enzyme. We therefore sought to create a new model with high penetrance colon-specific tumorigenesis but without the need for exogenous Cre administration. We utilized existing mice possessing a conditional knock out for the Apc gene and a latent activated Kras allele and crossed them with mice expressing Cre recombinase solely in the large intestine. Using this approach we generated mice that developed 1-9 colonic adenomas per mouse (average 4.3) but without any tumors in the small intestine or cecum. No invasive tumors were observed. Despite the apparent lack of invasion, the geographical correctness, complete penetrance and intermediate tumor burden make this model a promising addition to our toolkit for the study of colorectal cancer treatment and prevention.

Original languageEnglish
Pages (from-to)191-195
Number of pages5
JournalCancer Letters
Volume347
Issue number2
DOIs
StatePublished - 1 Jun 2014
Externally publishedYes

Keywords

  • Adenoma
  • Apc
  • Colorectal cancer
  • Kras
  • Mouse model
  • Tumor

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