title: Pin1 is required for ultraviolet A-stimulated cyclooxygenase-2 induction in mouse epidermal cells.
abstract: Ultraviolet A (UVA) radiation (320-400 nm) is considered a major cause of human skin photoaging and skin cancer. Overexpression of cyclooxygenase-2 (COX-2) leads to prostanoid formation in skin tissue, disturbs the balance between proliferation and apoptosis, and subsequently promotes tumorigenesis. The peptidyl-prolyl isomerase Pin1 is known to be overexpressed in most cancer cell types and plays an important role in oncogenesis. Here, we studied whether exposure of JB6 Cl41 mouse epidermal cells to UVA affects COX-2 expression and the possible involvement of Pin1 activation. UVA increased COX-2 protein expression and prostaglandin E2 production in an energy-dependent manner. Pre-exposure of JB6 Cl41 cells to UVA potentiated epidermal growth factor-induced anchorage-independent growth; this effect was significantly suppressed by inhibition of COX-2. UVA-stimulated COX-2 expression was significantly decreased by inhibition of Pin1. The increased COX-2 gene transcription in response to UVA was preceded by activation of the transcription factors nuclear factor-κB (NF-κB), cAMP response element-binding protein (CREB), CCAAT/enhancer-binding proteins α and β (C/EBPα and C/EBPβ) and c-Jun/activator protein-1 (AP-1). Pin1 inhibitor treatment suppressed the activation of NF-κB, CREB, and C/EBP by UVA irradiation. Conversely, JB6 C141 cells overexpressing Pin1 showed increased basal COX-2 expression and NF-κB, CREB, C/EBP, and AP-1 activities. These results suggest that UVA-induced COX-2 expression is mediated by Pin1 activation and this is associated with malignant transformation of epidermal cells.
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Bui Thu
authors: BT
authors: Quyen
authors: Hoo-Kyun
authors: HK
authors: Choi
authors: Keon Wook
authors: KW
authors: Kang
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000502:physiology; D004817:Epidermis / Q000201:enzymology / Q000473:pathology*; D004847:Epithelial Cells / Q000201:enzymology; D000077239:Meloxicam; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009285:Naphthoquinones / Q000494:pharmacology; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009285:Naphthoquinones; D013843:Thiazines; D013844:Thiazoles; D018808:Transcription Factor AP-1; D004815:Epidermal Growth Factor; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse; D015232:Dinoprostone; D000077239:Meloxicam; C005134:juglone