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

58 Citations (Scopus)

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

Fingerprint

troglitazone
Peroxisome Proliferator-Activated Receptors
Inbred C57BL Mouse
Colon
Carcinogenesis
Neoplasms
Gene Targeting
Large Intestine
Carcinogens
Colonic Neoplasms
Diet
Ligands

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: International Journal of Cancer, Vol. 116, No. 4, 10.09.2005, p. 495-499.

Research output: Contribution to journalArticle

@article{721108a5deb946e0be72946e9fd50061,
title = "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",
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.",
keywords = "Apc, Mlh1, PPAR-γ, Small intestine, colon, Thiazolidinediones, Troglitazone, Tumors",
author = "Kan Yang and Fan, {Kun Hua} and Lamprecht, {Sergio A.} and Winfried Edelmann and Levy Kopelovich and Raju Kucherlapati and Martin Lipkin",
year = "2005",
month = "9",
day = "10",
doi = "10.1002/ijc.21018",
language = "English (US)",
volume = "116",
pages = "495--499",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - 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

AU - Yang, Kan

AU - Fan, Kun Hua

AU - Lamprecht, Sergio A.

AU - Edelmann, Winfried

AU - Kopelovich, Levy

AU - Kucherlapati, Raju

AU - Lipkin, Martin

PY - 2005/9/10

Y1 - 2005/9/10

N2 - 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.

AB - 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.

KW - Apc

KW - Mlh1

KW - PPAR-γ

KW - Small intestine, colon

KW - Thiazolidinediones

KW - Troglitazone

KW - Tumors

UR - http://www.scopus.com/inward/record.url?scp=23244466054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23244466054&partnerID=8YFLogxK

U2 - 10.1002/ijc.21018

DO - 10.1002/ijc.21018

M3 - Article

VL - 116

SP - 495

EP - 499

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 4

ER -