Cyclooxygenase-2 Signaling in Squamous Cell Carcinomas

摘要: Cyclooxygenase-2 (COX-2) is the inducible isoform of enzymes that initiate prostaglandin synthesis from arachidonic acid. While COX-2 generally not expressed in most unperturbed adult tissues, it can be induced by multiple stimuli, including growth factors, cytokines, ultraviolet (UV) irradiation, tumor promoters and other stressors. Induction often involves transcriptional activation gene via transcription factor binding to cis-acting elements its promoter. overexpressed many epithelial cancers human mouse squamous cell carcinomas (SCCs). Mouse skin carcinogenesis models have been extensively used study molecular events involved SCC development. Inhibition activity with pharmacological agents, as well genetic manipulation expression levels transgenic knockout mice, demonstrated up-regulated expression/activity during promotion critically important for development tumors SCCs using both chemical UV protocols. PGE2, a major product signals through four G protein-coupled receptors, EP1-EP4, which show differential affinities PGE2 couple different proteins downstream signaling pathways. EP1, EP2, and/or EP4 shown induction tumors, keratinocyte proliferation, epidermal hyperplasia, inflammation angiogenesis.