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.
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.
Yang
Kan
K
Strang Cancer Research Laboratory at The Rockefeller University, New York, NY, USA.
Fan
Kun-Hua
KH
Lamprecht
Sergio A
SA
Edelmann
Winfried
W
Kopelovich
Levy
L
Kucherlapati
Raju
R
Lipkin
Martin
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000008:administration & dosage; D002352:Carrier Proteins; D002471:Cell Transformation, Neoplastic; D002839:Chromans / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000503:physiopathology / Q000662:veterinary; D004032:Diet; D017491:Genes, APC; D051379:Mice; D008810:Mice, Inbred C57BL; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D047495:PPAR gamma; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D002273:Carcinogens; D002352:Carrier Proteins; D002839:Chromans; C501486:MLH1 protein, human; C501485:Mlh1 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000070957:MutL Protein Homolog 1; D000077288:Troglitazone