Title

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

Document Type

Article

Publication Date

2006

Keywords

Colonic-Neoplasms, Disease-Progression, Female, Genes-APC, Genotype, Immunohistochemistry, Intestinal-Neoplasms, Male, Mice-Knockout, PPAR-gamma, Phenotype, Sex-Factors, Thiazoles, Thiazolidines

JAX Source

Int J Cancer 2006 Nov; 119(10):2339-46.

Abstract

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.