Expression of peroxisome proliferator-activated receptor delta in human gastric cancer and its response to specific COX-2 inhibitor.
Peroxisome proliferator-activated receptor delta (PPARdelta) is ligand-activated transcription factor of the nuclear receptor superfamily which is recently implicated in carcinogenesis. We examined the expression profiles of PPARdelta in human gastric cancer, normal gastric mucosa and gastric cancer cell lines by RT-PCR, Western blot and immunohistochemistry. PPARdelta 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 PPARdelta expression. In contrast, there was no suppression of PPARdelta in MKN28 gastric cell line with low COX-2 expression. Our results demonstrated the ubiquitous expression of PPARdelta in normal and cancer gastric epithelium. Suppression of PPARdelta may be one of the mechanisms underlying the chemopreventive effects of COX-2 inhibitor.
Yu
Jun
J
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, Hong Kong, China.
Leung
Wai K
WK
Chen
Jie
J
Ebert
Matthias P A
MP
Malfertheiner
Peter
P
Sung
Joseph J Y
JJ
D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D047495:PPAR gamma