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

Kan Yang, Kun Hua Fan, Sergio A. Lamprecht, Winfried Edelmann, Levy Kopelovich, Raju Kucherlapati, Martin Lipkin

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

The role of the nuclear peroxisome proliferator-activated receptor-γ (PPAR-γ) in colon tumorigenesis remains controversial. Notwithstanding evidence that PPAR-γ ligands impede murine colorectal carcinogenesis, PPAR-γ 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 pre-existing mutational events are not necessary for induction of colonic tumors by activated PPAR-γ in vivo.

Original languageEnglish (US)
Pages (from-to)495-499
Number of pages5
JournalInternational Journal of Cancer
Volume116
Issue number4
DOIs
StatePublished - Sep 10 2005

Keywords

  • Apc
  • Mlh1
  • PPAR-γ
  • Small intestine, colon
  • Thiazolidinediones
  • Troglitazone
  • Tumors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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