Role of c-Myc in intestinal tumorigenesis of the ApcMin/+ mouse

Cancer Biol Ther. 2006 Dec;5(12):1658-64. doi: 10.4161/cbt.5.12.3376. Epub 2006 Dec 7.


The c-MYC oncogene plays an important role in tumorigenesis and is commonly highly expressed in gastrointestinal cancers. In colon cells, c-MYC is regulated by the adenomatous polyposis coli (Apc) tumor suppressor gene. Multiple intestinal neoplasia (ApcMin/+ or Min) mice are heterozygous for a truncating Apc mutation and serve as a model of familial adenomatous polyposis (FAP) disease. To study the role of c-Myc in the mutant Apc-mediated colon tumorigenesis, we have developed a transgenic mouse with the conditional deletion of the floxed c-Myc alleles in the intestinal crypts of ApcMin/+ mice (ApcMin/+; c-Mycfl/fl). The floxed c-Myc deletion was initiated via a Cre recombinase controlled by the intestine-specific transcriptional regulatory elements of the liver fatty acid-binding protein gene (Fabpl4xat-132). Fabpl4xat-132-mediated Cre expression and recombination resulted in a two-fold decrease in c-MYC protein expression with no effect on intestinal tract morphology. Small intestinal tumorigenesis was significantly suppressed throughout the small intestinal tract of ApcMin/+; c-Mycfl/fl mice compared to c-Myc wild type littermates. In ApcMin/+; c-Mycfl/fl mice, the intestinal apoptosis was higher in the areas of the small intestine with the decreased c-Myc protein expression (P=0.0016, compared to their littermates with the wild type c-Myc). Thus, conditional inactivation of c-Myc, mediated by Fabpl4xat-132-driven Cre-recombinase, suppresses Apc-dependent intestinal tumorigenesis in adult ApcMin/+ mice, without apparent effect on normal intestinal mucosa.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Codon / genetics
  • Gene Deletion
  • Genes, APC*
  • Genes, myc*
  • Immunohistochemistry
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / pathology
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / pathology*
  • Intestine, Small / cytology
  • Intestine, Small / pathology
  • Mice
  • Mice, Knockout
  • Mutation
  • Proto-Oncogene Proteins c-myc / analysis
  • Sequence Deletion


  • Codon
  • Proto-Oncogene Proteins c-myc