Expression of peroxisome proliferator-activated receptors in human testicular cancer and growth inhibition by its agonists

Abstract

Objectives. To investigate the expression of peroxisome proliferator activator-receptor (PPAR)-alpha, beta, and gamma in human testicular cancer (TC) and normal testicular (NT) tissues, as well as the effects of the PPAR-gamma ligand. Recent studies have demonstrated that PPAR-gamma is expressed in various cancer tissues and its ligand induces growth arrest of these cancer cells through apoptosis. However, the expression of PPARs and the effects of PPAR-gamma ligand in testis have not been examined. Methods. Tumor specimens were obtained from 72 patients with TC. Specimens were obtained from 20 patients with NT tissue. The expressions were investigated using reverse transcriptase-polymerase chain reaction and immunohistochemical methods. We also investigated the inhibitory effect of the PPAR-gamma ligand on the TC-derived cell line. Results. Immunoreactive PPAR-alpha and beta were significantly apparent in TC tissues. Marked expression of PPAR-alpha and beta was also detected in the NT group. However, very weak or no expression of immunoreactive PPAR-gamma was found in the NT cases. In contrast, we found significant expression of immunoreactive PPAR-gamma in the cancer cells in the TC group. The synthetic PPAR-gamma agonists thiazolidinedione compounds and the endogenous PPAR-gamma ligand, 15-deoxy-Δ 12,14-prostaglandin J 2, inhibited the growth of the TC cells. Conclusions. PPAR-gamma is induced in TC, and the results suggest that PPAR-gamma ligands may mediate potent antiproliferative effects against TC cells through differentiation. Thus, PPAR-gamma may become a new target in the treatment of TC.