MUTATION AND EXPRESSION OF THE LOW-AFFINITY NEUROTROPHIN RECEPTOR IN HUMAN-MALIGNANT MELANOMA

The low affinity p75 neurotrophin receptor (p75(NTR)) is a cysteine-ri ch transmembrane glycoprotein which is frequently overexpressed in adv anced stages of human melanoma. The biological consequences of this ov erexpression are unknown; however, it has recently been shown that p75 (NTR) can enhance the invasive potential of melanoma cells in vitro. I n the present study we examined cell lines established from normal hum an melanocytes and metastatic melanomas for expression of p75(NTR) mRN A and protein. The results showed that, compared with normal melanocyt es, levels of p75(NTR)-specific protein were high in seven melanoma li nes, markedly decreased in two melanoma lines and comparable in two me lanoma lines. The conserved transmembrane domain of p75(NTR) was analy sed for point mutations by single strand conformation polymorphism ana lysis and direct DNA sequencing. Identical point mutations were detect ed in the transmembrane domain of p75(NTR) in the two melanoma lines w ith reduced p75(NTR) protein expression, which resulted in the substit ution of the uncharged amino acid Gly for the negatively-charged Asp.