Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists

Abstract

Recent studies have demonstrated that peroxisome proliferator activator-receptors(PPAR)-gamma is expressed in various cancer tissues and its ligand induces growth arrest of these cancer cells through apoptosis. In our study, we investigated the expression of PPAR-alpha, beta and gamma in human bladder tumor (BT) and normal bladder (NB) tissues as well as the effects of PPAR-gamma ligands. Specimens were obtained from 170 patients with BT and 20 with NB. The expressions were investigated using RT-PCR and immunohistochemical methods. We also investigated the inhibitory effect of PPAR-gamma ligands on BT-derived cell line. Immunoreactive PPAR-alpha and -beta were significantly apparent in both BT and NB tissues. Although no marked expression of PPAR-gamma was observed in NB tissue, significant expression was found in BT tissue. The extent and intensity of immunoreactive PPAR-gamma polypeptides in BT cells were statistically much greater than those of NB cells. Correlation between PPAR-gamma expression and tissue type or progression of bladder cancer was observed; PPAR-gamma expression was higher in G3 of bladder cancer than in G1 and was higher in advanced than in early cancer. PPAR-gamma agonists, troglitazone and 15-deoxy-Delta(12, 14)-prostaglandin J(2) inhibited the growth of the BT cells. PPAR-gamma is expressed in bladder tumor, and results suggest that PPAR-gamma ligands may mediate potent antiproliferative effects against BT cells. Thus, PPAR-gamma has the ability to become a new target in treatment of bladder tumor.