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      Differential expression of E prostanoid receptors in murine and human non-melanoma skin cancer.

      The Journal of Investigative Dermatology

      Animals, Carcinoma, Basal Cell, chemistry, Carcinoma, Squamous Cell, Cyclic AMP, analysis, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, therapeutic use, Female, Humans, Immunohistochemistry, Membrane Proteins, Mice, Mice, Hairless, Papilloma, Prostaglandin-Endoperoxide Synthases, RNA, Messenger, Receptors, Prostaglandin E, genetics, Receptors, Prostaglandin E, EP1 Subtype, Receptors, Prostaglandin E, EP2 Subtype, Receptors, Prostaglandin E, EP3 Subtype, Receptors, Prostaglandin E, EP4 Subtype, Skin Neoplasms

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          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.

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