Reference SummaryGirnun GD, Proc Natl Acad Sci U S A 2002 Oct 15;99(21):13771-6

Title

APC-dependent suppression of colon carcinogenesis by PPARgamma.

Authors

Girnun GD; Smith WM; Drori S; Sarraf P; Mueller E; Eng C; Nambiar P; Rosenberg DW; Bronson RT; Edelmann W; Kucherlapati R; Gonzalez FJ; Spiegelman BM

Journal

Proc Natl Acad Sci U S A

Volume

99

Issue

21

Year

2002

Pages

13771-6

Abstract

Activation of PPARgamma by synthetic ligands, such as thiazolidinediones, stimulates adipogenesis and improves insulin sensitivity. Although thiazolidinediones represent a major therapy for type 2 diabetes, conflicting studies showing that these agents can increase or decrease colonic tumors in mice have raised concerns about the role of PPARgamma in colon cancer. To analyze critically the role of this receptor, we have used mice heterozygous for Ppargamma with both chemical and genetic models of this malignancy. Heterozygous loss of PPARgamma causes an increase in beta-catenin levels and a greater incidence of colon cancer when animals are treated with azoxymethane. However, mice with preexisting damage to Apc, a regulator of beta-catenin, develop tumors in a manner insensitive to the status of PPARgamma. These data show that PPARgamma can suppress beta-catenin levels and colon carcinogenesis but only before damage to the APC/beta-catenin pathway. This finding suggests a potentially important use for PPARgamma ligands as chemopreventative agents in colon cancer.

Links

J:79682 – Mouse Genome Informatics
12370429 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Ppargtm1.1Gonz/+ Intestine - Large Intestine - Colon tumor
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

67 - 100

[not specified]-Ppargtm1.1Gonz/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0

[not specified] Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0

[not specified] Intestine - Large Intestine - Colon tumor
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

42 - 90

[not specified]-Apctm1Rak/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

65

[not specified]-Apctm1Rak/+ Ppargtm1.1Gonz/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

65

[not specified] Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0

[not specified]-Ppargtm1.1Gonz/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0