title: Differential expression of E prostanoid receptors in murine and human non-melanoma skin cancer.
abstract: Enhanced prostaglandin production via upregulated cyclooxygenase-2 (COX-2) expression is a likely contributing factor in ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), which consists primarily of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). The four E prostanoid (EP) receptors, designated EP1 through EP4, are known to bind prostaglandin E2 (PGE2), the major prostaglandin present in the skin. We used murine models of UVB-induced SCC and BCC, as well as human NMSC from sun-exposed sites, to investigate the expression of EP receptors during UVB-induced tumorigenesis. We observed that UVB-induced murine SCC are associated with markedly altered expression patterns of the EP receptors when compared with non-irradiated skin. In contrast, expression of all EP receptors was largely absent in UVB-induced murine BCC. We also observed expression of all four EP receptors in human SCC, with altered expression of their mRNA levels as compared with adjacent tumor-free skin. Consistent with our murine studies, no EP receptor expression was detected in human BCC, and their mRNA expression levels showed no change from the adjacent non-tumor-bearing skin. These data suggest that altered EP receptor expression may play a differential role in the development of UVB-induced SCC and BCC in murine and human skin.
authors.affiliation: Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Juliette Lois
authors.initials: JL
authors.lastname: Lee
authors.forename: Arianna
authors.initials: A
authors.lastname: Kim
authors.forename: Levy
authors.initials: L
authors.lastname: Kopelovich
authors.forename: David R
authors.initials: DR
authors.lastname: Bickers
authors.forename: Mohammad
authors.initials: M
authors.lastname: Athar
mesh_terms: D000818:Animals; D002280:Basal Cell Carcinoma / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000737:chemistry; D000242:Cyclic AMP / Q000032:analysis; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D051379:Mice; D008812:Mice, Hairless; D010212:Papilloma / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D018078:Receptors, Prostaglandin E / Q000032:analysis* / Q000235:genetics; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012878:Skin Neoplasms / Q000737:chemistry*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; C545635:PTGER1 protein, human; C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; C545650:PTGER4 protein, human; C545636:Ptger1 protein, mouse; C545645:Ptger2 protein, mouse; C545648:Ptger3 protein, mouse; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases