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.