title: Transcriptional regulation of Δ6-desaturase by peroxisome proliferative-activated receptor δ agonist in human pancreatic cancer cells: role of MEK/ERK1/2 pathway.
abstract: The Δ6-desaturase (Δ6D), 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 δ (PPAR δ ) agonist and MEK/ERK1/2-dependent pathway on the expression of Δ6D 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 δ agonist GW0742. Changes in mRNA and protein expression of Δ6D were then determined using real-time RT-PCR and Western blot, respectively. The expression of Δ6D (P < 0.01) increased following treatment with PPAR δ 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 Δ6D 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 δ and MEK/ERK1/2 signaling pathways affect differentially the expression of Δ6D in pancreatic cancer cells. Furthermore, there may be an inhibitory crosstalk between these two regulatory pathways on the mRNA expression of Δ6D and subsequently on Δ6D protein expression.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Darabi
authors.forename: Shima
authors.initials: S
authors.lastname: Byagowi
authors.forename: Shabnam
authors.initials: S
authors.lastname: Fayezi
authors.forename: Masoud
authors.initials: M
authors.lastname: Darabi
authors.forename: Shahab
authors.initials: S
authors.lastname: Mirshahvaladi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sahmani
mesh_terms: D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System; D047494:PPAR delta / Q000819:agonists*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D066246:ErbB Receptors; D044943:Fatty Acid Desaturases; D005419:Flavonoids; D047494:PPAR delta; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013844:Thiazoles; D020032:Tyrphostins; C101044:RTKI cpd; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds; C533241:FADS2 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one