{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:09:00Z","timestamp":1779124140588,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,5,8]],"date-time":"2006-05-08T00:00:00Z","timestamp":1147046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Protein kinase C (PKC) represents a large family of phosphatidylserine (PS)\u2010dependent serine\/threonine protein kinases. At least five PKC isoforms (\u03b1, \u03b4, \u03b5, \u03b7, and \u03b6) are expressed in epidermal keratinocytes. PKC isoforms are differentially expressed in proliferative (basal layer) and nonproliferative compartments (spinous, granular, cornified layers), which exhibit divergence in their roles in the regulation of epidermal cell proliferation, differentiation, and apoptosis. Immunocytochemical localization of PKC isoforms indicate that PKC\u03b1 is found in the membranes of suprabasal cells in the spinous and granular layers. PKC\u03b5 is mostly localized in the proliferative basal layers. PKC\u03b7 is localized exclusively in the granular layer. PKC\u03b4 is detected throughout the epidermis. PKC isozymes exhibit specificities in their signals to the development of skin cancer. PKC\u03b5, a calcium\u2010insensitive PKC isoform mediates the induction of squamous cell carcinoma (SCC) elicited either by the DMBA\u2010TPA protocol or by repeated exposures to ultraviolet radiation (UVR). PKC\u03b5 overexpression, which sensitizes skin to UVR\u2010induced carcinogenesis, suppresses UVR\u2010induced sunburn (apoptotic) cell formation, and enhances both UVR\u2010induced levels of TNF\u03b1 and hyperplasia. UVR\u2010induced sunburn cell formation is mediated by Fas\/Fas\u2010L and TNF\u03b1 NFR1 extrinsic apoptotic pathways. The death adaptor protein termed Fas\u2010associated death domain (FADD) is a common adaptor protein for both of these apoptotic pathways. PKC\u03b5 inhibits UVR\u2010induced expression of FADD leading to the inhibition of both apoptotic pathways. It appears that PKC\u03b5 sensitizes skin to the development of SCC by UVR by transducting signals, which inhibit apoptosis on one hand, and enhances proliferation of preneoplastic cells on the other hand. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20230","type":"journal-article","created":{"date-parts":[[2006,5,8]],"date-time":"2006-05-08T22:44:47Z","timestamp":1147128287000},"page":"381-388","source":"Crossref","is-referenced-by-count":49,"title":["Protein kinase C\u03b5 and development of squamous cell carcinoma, the nonmelanoma human skin cancer"],"prefix":"10.1002","volume":"45","author":[{"given":"Ajit K.","family":"Verma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deric L.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moammir 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