Troglitazone induction of COX-2 expression is dependent on ERK activation in keratinocytes.
Cyclooxygenase-2 (COX-2) plays an important role in tumorigenesis of several tissues, including skin. We report here that troglitazone, a thiazolidinedione class of antidiabetic drug, induced COX-2 expression at both the protein and mRNA levels and increased production of prostaglandin E2 (PGE2) in cultured keratinocytes. Troglitazone-induced COX-2 expression in keratinocytes was likely peroxisome proliferator-activated receptor gamma (PPARgamma)-independent. Troglitazone treatment of these cells also resulted in a sustained increase in phosphorylation of ERK. We show that induction of COX-2 by troglitazone was almost completely inhibited by specific inhibitors of ERK activation. These data suggest that troglitazone is capable of inducing COX-2 expression through an ERK-dependent mechanism in mouse skin keratinocytes.
He
Guobin
G
Department of Carcinogenesis, Science Park-Research Division, University of Texas M.D. Anderson Cancer Center, 1808 Park Road 1C, P.O. Box 389, Smithville, TX 78957, USA.
Sung
You Me
YM
Fischer
Susan M
SM
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D002839:Chromans; D005419:Flavonoids; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D045162:Thiazolidinediones; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077288:Troglitazone; D015232:Dinoprostone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one