Retinoids can be used to treat and prevent the formation of basal cell carcinoma (BCC) and squamous cell carcinomas (SCCs; notably cutaneous and oral SCC). Preferentially Expressed Antigen in Melanoma (PRAME), a gamete-specific repressor of retinoid-induced differentiation, is ectopically expressed in BCC and SCC tumors. However, the effects of PRAME on the development of these cancers and their sensitivity to retinoid therapies are unknown. The purpose of this study was to investigate PRAME’s influence on retinoid response and proliferation in benign human keratinocytes, BCC and SCC cells. To study the effect of PRAME on retinoid sensitivity, immortalized keratinocytes, BCC and SCC cells lines were manipulated using lentiviral vectors to either knock-down or overexpress PRAME, and then treated with all trans-retinoic acid (ATRA) or a vehicle. Expression of cytokeratins and other retinoid-responsive genes was assessed by immunoblotting and RT-qPCR. Overexpression of PRAME in HaCaT keratinocytes and in SCC cells impaired ATRA-induced changes in cytokeratin expression. Consistently, PRAME knockdown in an SCC cell line enhanced ATRA-induced changes in cytokeratin expression. Immunoblotting for cell cycle proteins, Ki-67 immunocytochemistry and cell cycle flow cytometry analysis with propidium iodide/RNAse staining were used to evaluate cell cycle progression and proliferation. PRAME overexpression resulted in decreased levels of p14/ARF and p27/Kip1 protein, whilst the opposite effect was observed in PRAME knockdown cells. This result would suggest that PRAME is an active participant in cell cycle regulation. Importantly, the anti-proliferative activity of ATRA was impaired in PRAME-overexpressing cells, but enhanced in PRAME knockdown cells relative to controls. Our data suggests that PRAME modulates the cell cycle and sensitivity to retinoid therapies in benign and malignant keratinocytes. PRAME may represent a putative biomarker or therapeutic target to investigate further.

ESDR468 - Preferentially Expressed Antigen in Melanoma Modulates Sensitivity to Retinoic Acid and Cell Cycle Control in Immortalized and Malignant Keratinocytes

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.