Peroxisome proliferator-activated receptor gamma agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638 N/+ Mlh1+/- double mutant mice

Int J Cancer. 2005 Sep 10;116(4):495-9. doi: 10.1002/ijc.21018.


The role of the nuclear peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in colon tumorigenesis remains controversial. Notwithstanding evidence that PPAR-gamma ligands impede murine colorectal carcinogenesis, PPAR-gamma agonists have been shown to enhance in vivo tumor formation in mouse models of human colon cancer. Our study was designed to determine whether troglitazone (TGZ) induces colonic tumor formation in normal C57BL/6J mice and enhances colorectal carcinogenesis in double mutant Apc1638N/+ Mlh1+/- mice fed a standard AIN-76A diet. We report herein that not only does TGZ enhance carcinogenesis in the large intestine of mutant mice predisposed to intestinal carcinogenesis but TGZ also induces colonic tumors in normal mice without gene targeting or carcinogen administration. This observation indicates that preexisting mutational events are not necessary for induction of colonic tumors by activated PPAR-gamma in vivo.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinogens / administration & dosage
  • Carrier Proteins
  • Cell Transformation, Neoplastic
  • Chromans / pharmacology*
  • Colonic Neoplasms / chemically induced*
  • Colonic Neoplasms / physiopathology
  • Colonic Neoplasms / veterinary
  • Diet
  • Genes, APC
  • Mice
  • Mice, Inbred C57BL
  • MutL Protein Homolog 1
  • Mutation
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / genetics
  • PPAR gamma
  • Thiazolidinediones / pharmacology*
  • Troglitazone


  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Carcinogens
  • Carrier Proteins
  • Chromans
  • MLH1 protein, human
  • Mlh1 protein, mouse
  • Neoplasm Proteins
  • Nuclear Proteins
  • PPAR gamma
  • Thiazolidinediones
  • MutL Protein Homolog 1
  • Troglitazone