The Department of Molecular Carcinogenesis, Science Park, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Cancer Metastasis Rev. 2011 Dec;30(3-4):465-80. doi: 10.1007/s10555-011-9317-9.
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.
皮肤暴露于紫外 (UV) 光的最常见特征之一是引发炎症，炎症是肿瘤发生的一个促成因素，其特征是细胞因子、生长因子和花生四烯酸代谢物的合成，包括前列腺素 (PGs)。对 PG 在非黑素瘤皮肤癌 (NMSC) 中的作用的研究表明，环氧合酶 (COX) 的 COX-2 同工型负责 PGE(2) 的大多数病理效应。在小鼠皮肤模型中，COX-2 缺乏可显著预防化学致癌剂或 UV 诱导的 NMSC，而过表达则赋予内源性肿瘤促进活性。目前的研究集中于确定介导 PGE(2) 的肿瘤促进/进展活性的 G 蛋白偶联 EP 受体以及涉及的信号通路。如本文所述，EP1、EP2 和 EP4 受体，但不是 EP3 受体，有助于 NMSC 的发展，尽管通过不同的信号通路并具有不同的结果。特定 EP 受体激活的信号通路具有特定的上下文依赖性，可能取决于 PGE(2) 合成的水平、不同 EP 受体的表达水平以及其他相互作用受体的表达水平。了解 EP 受体的作用和作用机制可能为 NMSC 的预防或治疗提供新的靶点。
