Genetic disruption of PPAR delta decreases the tumorigenicity of human colon cancer cells

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone rec eptors that have been implicated in a variety of biologic processes. The PP AR delta isotype was recently proposed as a downstream target of the adenom atous polyposis coli (APC)/beta catenin pathway in colorectal carcinogenesi s. To evaluate its role in tumorigenesis, a PPAR delta null cell line was c reated by targeted homologous recombination. When inoculated as xenografts in nude mice, PPAR delta -/- cells exhibited a decreased ability to form tu mors compared with PPAR delta +/- and wild-type controls. These data sugges t that suppression of PPAR delta expression contributes to the growth-inhib itory effects of the APC tumor suppressor.