Reference SummaryLefebvre AM, Nat Med 1998 Sep;4(9):1053-7

Title

Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice.

Authors

Lefebvre AM; Chen I; Desreumaux P; Najib J; Fruchart JC; Geboes K; Briggs M; Heyman R; Auwerx J

Journal

Nat Med

Volume

4

Issue

9

Year

1998

Pages

1053-7

Abstract

The development of colorectal cancer, one of the most frequent cancers, is influenced by prostaglandins and fatty acids. Decreased prostaglandin production, seen in mice with mutations in the cyclooxygenase 2 gene or in animals and humans treated with cyclooxygenase inhibitors, prevents or attenuates colon cancer development. There is also a strong correlation between the intake of fatty acids from animal origin and colon cancer. Therefore, the peroxisome proliferator-activated receptor gamma (PPARgamma), a downstream transcriptional mediator for prostaglandins and fatty acids which is highly expressed in the colon may be involved in this process. Activation of PPARgamma by two different synthetic agonists increased the frequency and size of colon tumors in C57BL/6J-APCMin/+ mice, an animal model susceptible to intestinal neoplasia. Tumor frequency was only increased in the colon, and did not change in the small intestine, coinciding with the colon-restricted expression of PPARgamma. Treatment with PPARgamma agonists increased beta-catenin levels both in the colon of C57BL/61-APCMin/+ mice and in HT-29 colon carcinoma cells. Genetic abnormalities in the Wnt/wingless/APC pathway, which enhance the transcriptional activity of the beta-catenin-T-cell factor/lymphoid enhancer factor 1 transcription complex, often underly the development of colon tumors. Our data indicate that PPARgamma activation modifies the development of colon tumors in C57BL/61-APCMin/+ mice.

Links

J:49814 – MGI References
9734399 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C57BL/6J-ApcMin/+ Mice were purchased from The Jackson Laboratory.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon adenocarcinoma
  • BRL-49,653, PPAR gamma ligand
Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon adenoma - tubular Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor
  • BRL-49,653, PPAR gamma ligand
Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor
  • troglitazone
Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Distal tumor
  • BRL-49,653, PPAR gamma ligand
Intestine - Small Intestine - Distal

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Distal tumor Intestine - Small Intestine - Distal

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Distal tumor
  • troglitazone
Intestine - Small Intestine - Distal

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Proximal tumor
  • BRL-49,653, PPAR gamma ligand
Intestine - Small Intestine - Proximal

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Proximal tumor Intestine - Small Intestine - Proximal

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Proximal tumor
  • troglitazone
Intestine - Small Intestine - Proximal

observed

C57BL/6J-ApcMin/+ Intestine tumor
  • BRL-49,653, PPAR gamma ligand
Intestine

observed

C57BL/6J-ApcMin/+ Intestine tumor Intestine

observed

C57BL/6J-ApcMin/+ Intestine tumor
  • troglitazone
Intestine

observed