Expression of peroxisome proliferator-activated receptor δ in human gastric cancer and its response to specific COX-2 inhibitor

Abstract

Peroxisome proliferator-activated receptor δ (PPARδ) is ligand-activated transcription factor of the nuclear receptor superfamily which is recently implicated in carcinogenesis. We examined the expression profiles of PPARδ in human gastric cancer, normal gastric mucosa and gastric cancer cell lines by RT-PCR, Western blot and immunohistochemistry. PPARδ mRNA and protein was found to be ubiquitously expressed in all 5 gastric cancer cell lines, 40 gastric cancer samples and 10 normal gastric mucosa from non-cancer patients. Positive immunoreactivity was detected in the nuclei of normal and malignant gastric epithelium. Treatment of gastric cell line MKN45 that overexpressed cyclooxygenase-2 (COX-2) with specific COX-2 inhibitor NS398 resulted in a time- and dose-dependent suppression of PPARδ expression. In contrast, there was no suppression of PPARδ in MKN28 gastric cell line with low COX-2 expression. Our results demonstrated the ubiquitous expression of PPARδ in normal and cancer gastric epithelium. Suppression of PPARδ may be one of the mechanisms underlying the chemopreventive effects of COX-2 inhibitor.