Intestinal-specific PPARgamma deficiency enhances tumorigenesis in ApcMin/+ mice

Int J Cancer. 2006 Nov 15;119(10):2339-46. doi: 10.1002/ijc.22115.


Multiple investigations of the effects of peroxisome proliferator-activated receptor gamma (PPARgamma) ligands on colon cancer have produced contradictory results. While some studies demonstrated increased numbers of colonic polyps in Apc(Min/+) mice treated with various thiazolidinedione (TZD) PPARgamma ligands, others reported amelioration of tumor multiplicity and progression in both Apc(Min/+) mice and in mice with chemically-induced colon cancer. Here, we addressed the role of PPARgamma in murine intestinal tumorigenesis using gene knockout methodology. We found that either heterozygous or homozygous intestinal-specific PPARgamma deficiency enhanced the number of Apc(Min/+) tumors in both the small intestine and colon, especially in the colon, where PPARgamma deficiency also modulated tumor incidence. Gender significantly affected tumor multiplicity independent of PPARgamma genotype. Female Apc(Min/+) mice developed more tumors in the small intestine and more tumors overall, whereas male Apc(Min/+) mice developed more tumors in the colon. Nevertheless, intestinal PPARgamma deficiency enhanced tumorigenesis irrespective of gender. Our results suggest that PPARgamma functions as a tumor resistance factor in the mouse intestine and warrant further investigation of the PPARgamma-dependent and independent actions of TZDs in cancer.

Publication types

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

MeSH terms

  • Animals
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Disease Progression
  • Female
  • Genes, APC*
  • Genotype
  • Immunohistochemistry
  • Intestinal Neoplasms / genetics
  • Intestinal Neoplasms / metabolism*
  • Intestinal Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Knockout
  • PPAR gamma / deficiency*
  • PPAR gamma / genetics
  • Phenotype
  • Sex Factors
  • Thiazoles / metabolism*
  • Thiazolidines


  • PPAR gamma
  • Thiazoles
  • Thiazolidines
  • thiazoline-2-thione