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

Natalia A. Ignatenko, Hana Holubec, David G. Besselsen, Karen A. Blohm-Mangone, Jose L. Padilla-Torres, Raymond B. Nagle, Ignacio Moreno De Alboránç, Jose M. Guillen-R, Eugene W. Gerner

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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 Apc Min/+ 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.

Original languageEnglish (US)
Pages (from-to)1658-1664
Number of pages7
JournalCancer Biology and Therapy
Volume5
Issue number12
DOIs
StatePublished - Dec 2006

Keywords

  • Apc Min/+ mouse
  • FAP
  • Intestinal tumorigenesis
  • Intestine-specific knockout
  • Mouse model
  • c-Myc oncogene

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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