Gene alterations by peroxisome proliferator-activated receptor γ agonists in human colorectal cancer cells

Abstract

The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear transcription factor that controls the genes involved in metabolism and carcinogenesis. In the present study, we examined the alteration of gene expression in HCT-116 human colorectal cancer cells by PPARγ agonists: MCC-555 (5 μM), rosiglitazone (5 μM), and 15-deoxy-Δ12,14-prostaglandin J2 (1 μM). The long-oligo microarray data revealed a list of target genes commonly induced (307 genes) and repressed (32 genes) by tested PPARγ agonists. These genes were analyzed by Onto-Express software and KEGG pathway analysis and revealed that PPARγ agonists are involved in cell proliferation, focal adhesion, and several signaling pathways. Eight genes were selected to confirm the microarray data by RT-PCR and real-time PCR, from which CSTA, DAP13, TAF12, RIS1, CDKN3 and MAGOH were up-regulated, and KLHL11 and NCOA2 were down-regulated. This study elucidates the commonly induced genes modulated by tested PPARγ ligands involved in the different signaling pathways and metabolisms, probably mediated in a PPARγ-dependent manner in colorectal cancer cells and helps to better understand the pleiotropic actions of PPARγ ligands.