Transcriptional Regulation of Delta 6-Desaturase by Peroxisome Proliferative-Activated Receptor delta Agonist in Human Pancreatic Cancer Cells: Role of MEK/ERK1/2 Pathway

Abstract

The Delta 6-desaturase (Delta 6D), also known as fatty acid desaturase 2, is a regulatory enzyme in de novo fatty acid synthesis, which has been linked to obesity and diabetes. The aim of the present study was to investigate the effect of peroxisome proliferative-activated receptor delta (PPAR delta) agonist and MEK/ERK1/2-dependent pathway on the expression of Delta 6D in human pancreatic carcinoma cell line PANC-1. PANC-1 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPAR delta agonist GW0742. Changes in mRNA and protein expression of Delta 6D were then determined using real-time RT-PCR and Western blot, respectively. The expression of Delta 6D (P < 0.01) increased following treatment with PPAR delta agonist both at mRNA and protein levels, whereas no significant change was observed after treatment with MEK/ERK1/2 pathway inhibitor. It was also found that the increase in the expression of Delta 6D in response to GW0742 was significantly inhibited by PD98059 (>40%, P < 0.05) or EGF receptor-selective inhibitor AG1478 (>25%, P < 0.05) pretreatment. PPAR delta and MEK/ERK1/2 signaling pathways affect differentially the expression of Delta 6D in pancreatic cancer cells. Furthermore, there may be an inhibitory crosstalk between these two regulatory pathways on the mRNA expression of Delta 6D and subsequently on Delta 6D protein expression.