Role for PPARγ and PPARδ in colonic carcinogenesis

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Peroxisome proliferator-activated receptor (PPAR) is a family of nuclear receptors and three subtypes of PPAR are known at present, PPARα, PPARδ, and PPARγ. Since recent reports suggest the involvement of PPAR in the regulation of cell proliferation, differentiation, and cell death, we studied the effect of PPAR ligands in colonic epithelial cells and obtained the following results. (1) PPARγ ligands suppressed cell growth response in colonic cancer cell lines and induced apoptosis. (2) cDNA array experiments revealed that PPARγ-induced cell growth suppression is associated with the downregulation of c-myc expression and upregulation of c-jun and gadd153 expression. (3) hTERT, of which expression is reported to be regulated by c-myc, was also downregulated by PPARγ ligands. (4) PPARα and PPARδ ligands had no significant effects on cell growth response in colonic cancer cell lines.