Target genes of peroxisome proliferator-activated receptor γ in colorectal cancer cells

Activation of the nuclear hormone peroxisome proliferator-activated receptor gamma (PPAR gamma) inhibits cell growth and promotes differentiation in a broad spectrum of epithelial derived tumor cell lines. Here we utilized microarray technology to identify PPAR gamma gene targets in intestinal epithelial cells. For each gene, the induction or repression was seen with two structurally distinct PPAR gamma agonists, and the change in expression could be blocked by co-treatment with a specific PPAR gamma antagonist. A majority of the genes could be regulated independently by a retinoid X receptor specific agonist. Genes implicated in lipid transport or storage (adipophilin and liver fatty acid-binding protein) were also activated by agonists of PPAR subtypes alpha and/or delta. In contrast, PPAR gamma -selective targets included genes linked to growth regulatory pathways (regenerating gene IA), colon epithelial cell maturation (GOB-4 and keratin 20), and immune modulation (neutrophil-gelatinase-associated lipocalin). Additionally, three different genes of the carcinoembryonic antigen family were induced by PPAR gamma. Cultured cells treated with PPAR gamma ligands demonstrated an increase in Ca2+-independent, carcinoembryonic antigen-dependent homotypic aggregation, suggesting a potential role for PPAR gamma in regulating intercellular adhesion. Collectively, these results will help define the mechanisms by which PPAR gamma regulates intestinal epithelial cell biology.