Vitamin A metabolism and mRNA expression of retinoid-binding protein and receptor genes in human epidermal melanocytes and melanoma cells

Retinoids inhibit proliferation of melanocytes and melanoma cells and affect disorders of hypo-and hyperpigmentation, Such effects might involve retinoid-binding proteins, retinoid metabolites and nuclear retinoid receptors for transcriptional activation, We detected messenger RNA transcripts for the cellular retinol-and retinoic acid-binding proteins (CRBP, CRABP I and II) in cultured epidermal melanocytes, In the melanoma cell lines the major transcript was CRABP II, Nuclear retinoic acid (RA) receptor transcripts and the 9-cis-retinoic acid receptor transcript were detected in all cells, The endogenous concentrations of retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) in melanocytes were five times those in melanoma cells. When cells were incubated with [H-3]ROH the main metabolites in the melanocytes were [H-3]ddROH (4%) and [H-3]RA (0.4%), Formation of [H-3]RA was only detected in one melanoma cell line. Both melanocytes and melanoma cells produced an unidentified metabolite when incubated with [3H]ROH and [H-3]RA, Dissimilarities in the metabolism and endogenous concentration of retinoids between benign and malignant melanocytes might play a key role in differentiation and growth regulation.