Genetic disruption of PPARδ decreases the tumorigenicity of human colon cancer cells

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that have been implicated in a variety of biologic processes. The PPAR delta isotype was recently proposed as a downstream target of the adenomatous polyposis coli (APC)/beta catenin pathway in colorectal carcinogenesis. To evaluate its role in tumorigenesis, a PPAR delta null cell line was created by targeted homologous recombination. When inoculated as xenografts in nude mice, PPAR delta -/- cells exhibited a decreased ability to form tumors compared with PPAR delta +/- and wild-type controls. These data suggest that suppression of PPAR delta expression contributes to the growth-inhibitory effects of the APC tumor suppressor.