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

Activation of the nuclear hormone peroxisome proliferator-activated recepto r gamma (PPAR gamma) inhibits cell growth and promotes differentiation in a broad spectrum of epithelial derived tumor cell lines. Here we utilized mi croarray technology to identify PPAR gamma gene targets in intestinal epith elial cells. For each gene, the induction or repression was seen with two s tructurally distinct PPAR gamma agonists, and the change in expression coul d be blocked by co-treatment with a specific PPAR gamma antagonist. A major ity of the genes could be regulated independently by a retinoid X receptor specific agonist. Genes implicated in lipid transport or storage (adipophil in and liver fatty acid-binding protein) were also activated by agonists of PPAR subtypes alpha and/or delta. In contrast, PPAR gamma -selective targe ts included genes linked to growth regulatory pathways (regenerating gene I A), colon epithelial cell maturation (GOB-4 and keratin 20), and immune mod ulation (neutrophil-gelatinase-associated lipocalin). Additionally, three d ifferent genes of the carcinoembryonic antigen family were induced by PPAR gamma. Cultured cells treated with PPAR gamma ligands demonstrated an incre ase in Ca2+-independent, carcinoembryonic antigen-dependent homotypic aggre gation, suggesting a potential role for PPAR gamma in regulating intercellu lar adhesion. Collectively, these results will help define the mechanisms b y which PPAR gamma regulates intestinal epithelial cell biology.