PPAR delta status and mismatch repair mediated neoplasia in the mouse intestine

Reed, K., Sansom, O. , Hayes, A., Gescher, A., Peters, J. and Clarke, A. (2006) PPAR delta status and mismatch repair mediated neoplasia in the mouse intestine. BMC Cancer, 6, p. 113. (doi: 10.1186/1471-2407-6-113)

Abstract

Background: Therapeutic regulation of PPAR delta activity using selective agonists has been proposed for various disorders. However, the consequences of altered peroxisome proliferator-activated receptor delta ( PPAR delta) activity in the context of intestinal tumourigenesis remain somewhat unclear. Contradictory evidence suggesting PPAR delta either attenuates or potentiates intestinal neoplasia. To further investigate the PPARd dependency of intestinal tumourigenesis, we have analysed the consequences of PPAR delta deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair. Methods: Mice deficient for both PPAR delta and the mismatch repair gene Mlh1 were produced and the incidence and severity of intestinal neoplasia recorded. Results: No significant differences between the control genotypes and the double mutant genotypes were recorded indicating that deficiency of PPAR delta does not modify impaired mismatch repair induced neoplasia. Conclusion: In contrast with the previously observed acceleration of intestinal neoplasia in the context of the Apc(Min/+) mouse, PPAR delta deficiency does not alter the phenotype of mismatch repair deficiency. This data supports the notion that PPAR delta is not required for adenoma formation and indicate that any pro-tumourigenic effect of PPAR delta inactivation may be highly context dependent.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sansom, Professor Owen
• Authors: Reed, K., Sansom, O., Hayes, A., Gescher, A., Peters, J., and Clarke, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: BMC Cancer
• Publisher: BioMed Central Ltd.
• ISSN: 1471-2407