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

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