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 [3H]ROH the main metabolites in the melanocytes were [3H]ddROH (4%) and [3H]RA (0.4%). Formation of [3H]RA was only detected in one melanoma cell line. Both melanocytes and melanoma cells produced an unidentified metabolite when incubated with [3H]ROH and [3H]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.
Rosdahl
I
I
Department of Dermatology, University Hospital, Linköping, Sweden.
Andersson
E
E
Kågedal
B
B
Törmä
H
H
D002478:Cells, Cultured; D002648:Child; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D012177:Retinol-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D054840:Retinol-Binding Proteins, Cellular; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured; D014801:Vitamin A / Q000378:metabolism*
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; C027928:retinol binding protein receptor; D014316:Tritium; D014801:Vitamin A; D014212:Tretinoin