Mutation and expression of the low affinity neurotrophin receptor in human malignant melanoma

The low affinity p75 neurotrophin receptor (p75NTR) is a cysteine-rich transmembrane glycoprotein which is frequently overexpressed in advanced stages of human melanoma. The biological consequences of this overexpression are unknown; however, it has recently been shown that p75NTR can enhance the invasive potential of melanoma cells in vitro. In the present study we examined cell lines established from normal human melanocytes and metastatic melanomas for expression of p75NTR mRNA and protein. The results showed that, compared with normal melanocytes, levels of p75NTR-specific protein were high in seven melanoma lines, markedly decreased in two melanoma lines and comparable in two melanoma lines. The conserved transmembrane domain of p75NTR was analysed for point mutations by single strand conformation polymorphism analysis and direct DNA sequencing. Identical point mutations were detected in the transmembrane domain of p75NTR in the two melanoma lines with reduced p75NTR protein expression, which resulted in the substitution of the uncharged amino acid Gly for the negatively-charged Asp.