Importance of the EP(1) receptor in cutaneous UVB-induced inflammation and tumor development.
Chronic exposure to UV light, the primary cause of skin cancer, results in the induction of high levels of cyclooxygenase-2 (COX-2) expression in the skin. The involvement of COX-2 in the carcinogenesis process is mediated by its enzymatic product, prostaglandin E(2) (PGE(2)). PGE(2) has been shown to have a variety of activities that can contribute to tumor development and growth. The effects of PGE(2) on different cell types are mediated by four E prostanoid (EP) receptors, EP(1)-EP(4). While recent studies have demonstrated the importance of EP(1) in the development of colon and breast cancer, the extent of EP(1) involvement in the cutaneous photocarcinogenesis process is unknown. This study found that topical treatment with celecoxib or the specific EP(1) antagonist ONO-8713 decreased acute UVB-induced inflammation in the skin and significantly reduced the number of tumors per mouse following 25 weeks of UVB exposure and topical treatment. This study suggests that drugs designed to block EP(1) may have the potential to be used as anti-inflammatory and/or chemopreventive agents that reduce the risk of skin cancer development.
Tober
Kathleen L
KL
Department of Pathology, The Ohio State University, Columbus, Ohio 43210, USA.
Wilgus
Traci A
TA
Kusewitt
Donna F
DF
Thomas-Ahner
Jennifer M
JM
Maruyama
Takayuki
T
Oberyszyn
Tatiana M
TM
D000818:Animals; D000068579:Celecoxib; D002934:Cinnamates / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D003872:Dermatitis / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D015603:Keratinocytes / Q000737:chemistry; D051379:Mice; D008812:Mice, Hairless; D011720:Pyrazoles / Q000627:therapeutic use; D018078:Receptors, Prostaglandin E / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000209:etiology*; D013449:Sulfonamides / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014466:Ultraviolet Rays
D002934:Cinnamates; D016861:Cyclooxygenase Inhibitors; C411295:ONO 8713; C545636:Ptger1 protein, mouse; D011720:Pyrazoles; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; D000068579:Celecoxib