Expression of the MC1 receptor gene in normal and malignant human melanocytes. A semiquantitative RT-PCR study.
Alpha melanocyte-stimulating hormone (MSH) and related proopiomelanocortin-derived (POMC) peptides bind to the melanocortin 1 receptor (MC1-R) of mammalian melanocytes and stimulate proliferation and melanogenesis. POMC transcripts and alpha-MSH-like immunoreactivity have been found in melanoma cells and a possible autocrine loop involving MC1-R and POMC-derived products has been proposed. Therefore, the alpha-MSH/MC1-R system plays a major role in the biology of melanocytes, and provides targets for melanoma diagnosis and therapy. However, the relative levels of MC1-R expression in normal melanocytes (NM) and melanoma cells are unknown, and it is still debated whether or not all human melanomas express the MC1-R. We describe a semiquantitative RT-PCR assay for MC1-R expression, using a competition vector generated by deleting 164 bp of the native gene. The competitor was employed to analyse a panel of human melanoma cells, tumour samples, giant congenital nevus cells (CNM) and normal melanocytes (NM). All samples were positive for MC1-R expression, but expression of the receptor gene did not correlate with that of tyrosinase. Expression levels were about 10 and 20 times higher for surgical specimens and cultured melanoma cells, respectively, than for NM, but comparable for CNM and NM. Thus, high MC1-R expression is a frequent event in malignant melanocytes, and might lead to a higher activity of the alpha-MSH/MC1-R system in melanoma cells as compared to normal melanocytes, for equal local concentrations of the hormone or related melanocortins.
Loir
B
B
Dept. of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Espinardo, Spain.
Pérez Sánchez
C
C
Ghanem
G
G
Lozano
J A
JA
García-Borrón
J C
JC
Jiménez-Cervantes
C
C
D001667:Binding, Competitive; D015152:Blotting, Northern; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009508:Nevus, Pigmented / Q000151:congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011333:Pro-Opiomelanocortin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D011979:Receptors, Pituitary Hormone / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D012878:Skin Neoplasms / Q000151:congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D000521:alpha-MSH / Q000494:pharmacology
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011979:Receptors, Pituitary Hormone; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; C029446:MSH receptor; D014442:Monophenol Monooxygenase