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 mamm alian melanocytes and stimulate proliferation and melanogenesis. POMC trans cripts and a-MSH-like immunoreactivity have been found in melanoma cells an d a possible autocrine loop involving MC1-R and POMC-derived products has b een proposed. Therefore, the alpha-MSH/MC1-R system plays a major role in t he biology of melanocytes, and provides targets for melanoma diagnosis and therapy. However, the relative levels of MC1-R expression in normal melanoc ytes (NM) and melanoma cells are unknown, and it is still debated whether o r 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 ce lls (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 sur gical 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.