Papandreou C, Bogenrieder T, Loganzo F, Chao M V, Nanus D M, Albino A P
Laboratory of Mammalian Cell Transformation, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Melanoma Res. 1996 Oct;6(5):373-8. doi: 10.1097/00008390-199610000-00004.
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.
低亲和力神经营养因子受体（p75NTR）是一种富含半胱氨酸的跨膜糖蛋白，在人类黑色素瘤晚期常过度表达。这种过度表达的生物学后果尚不清楚；然而，最近有研究表明，p75NTR可增强黑色素瘤细胞在体外的侵袭能力。在本研究中，我们检测了从正常人黑素细胞和转移性黑色素瘤建立的细胞系中p75NTR mRNA和蛋白的表达情况。结果显示，与正常黑素细胞相比，7个黑色素瘤细胞系中p75NTR特异性蛋白水平较高，2个黑色素瘤细胞系中明显降低，2个黑色素瘤细胞系中相当。通过单链构象多态性分析和直接DNA测序对p75NTR保守的跨膜结构域进行点突变分析。在p75NTR蛋白表达降低的两个黑色素瘤细胞系的跨膜结构域中检测到相同的点突变，该突变导致带负电荷的天冬氨酸被不带电荷的甘氨酸取代。
