VITAMIN-A METABOLISM AND MESSENGER-RNA EXPRESSION OF RETINOID-BINDINGPROTEIN 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 inv olve retinoid-binding proteins, retinoid metabolites and nuclear retin oid receptors for transcriptional activation, We detected messenger RN A transcripts for the cellular retinol-and retinoic acid-binding prote ins (CRBP, CRABP I and II) in cultured epidermal melanocytes, In the m elanoma cell lines the major transcript was CRABP II, Nuclear retinoic acid (RA) receptor transcripts and the 9-cis-retinoic acid receptor t ranscript were detected in all cells, The endogenous concentrations of retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) in mela nocytes were five times those in melanoma cells. When cells were incub ated with [H-3]ROH the main metabolites in the melanocytes were [H-3]d dROH (4%) and [H-3]RA (0.4%), Formation of [H-3]RA was only detected i n one melanoma cell line. Both melanocytes and melanoma cells produced an unidentified metabolite when incubated with [3H]ROH and [H-3]RA, D issimilarities in the metabolism and endogenous concentration of retin oids between benign and malignant melanocytes might play a key role in differentiation and growth regulation.