The role of the EP receptors for prostaglandin E2 in skin and skin cancer.
One of the most common features of exposure of skin to ultraviolet (UV) light is the induction of inflammation, a contributor to tumorigenesis, which is characterized by the synthesis of cytokines, growth factors and arachidonic acid metabolites, including the prostaglandins (PGs). Studies on the role of the PGs in non-melanoma skin cancer (NMSC) have shown that the cyclooxygenase-2 (COX-2) isoform of the cyclooxygenases is responsible for the majority of the pathological effects of PGE(2). In mouse skin models, COX-2 deficiency significantly protects against chemical carcinogen- or UV-induced NMSC while overexpression confers endogenous tumor promoting activity. Current studies are focused on identifying which of the G protein-coupled EP receptors mediate the tumor promotion/progression activities of PGE(2) and the signaling pathways involved. As reviewed here, the EP1, EP2, and EP4 receptors, but not the EP3 receptor, contribute to NMSC development, albeit through different signaling pathways and with somewhat different outcomes. The signaling pathways activated by the specific EP receptors are context specific and likely depend on the level of PGE(2) synthesis, the differential levels of expression of the different EP receptors, as well as the levels of expression of other interacting receptors. Understanding the role and mechanisms of action of the EP receptors potentially offers new targets for the prevention or therapy of NMSCs.
The Department of Molecular Carcinogenesis, Science Park, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
J E
JE
Rundhaug
M S
MS
Simper
I
I
Surh
S M
SM
Fischer
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D018078:Receptors, Prostaglandin E; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone