Suppression of proto-oncogene (AP-1) in a model of skin epidermal hyperproliferation is reversed by topical application of 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatrienoic acid.
The present study was conducted to delineate whether a possible mechanism for 13-(S)-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatrienoic acid (15-HETrE) reversal of experimentally-induced skin hyperproliferation in guinea pig is via the modulation of epidermal nuclear mitogen activator protein (AP-1), a nuclear transcription factor associated with tissue turnover. The data revealed that topical application of 13-HODE and/or 15-HETrE on the induced hyperproliferative skin reversed the hyperproliferation and up-regulated the suppressed AP-1 expression. A further analysis of the two major subunits of AP-1 (c-fos and c-jun) revealed a selective up-regulation of c-fos. These results underscore the modulatory role of lipoxygenase-derived hydroxy fatty acids on nuclear transcription factors and explains, at least in part, the antiproliferative effects of 13-HODE and 15-HETrE.
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Department of Dermatology, School of Medicine, University of California at Davis, 95616, USA.
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D000287:Administration, Topical; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004357:Drug Synergism; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008041:Linoleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000166:cytology*; D018808:Transcription Factor AP-1 / Q000235:genetics*
D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D004281:Docosahexaenoic Acids; C024348:13-hydroxy-9,11-octadecadienoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid