Halaban R, Fan B, Ahn J, Funasaka Y, Gitay-Goren H, Neufeld G
Yale University School of Medicine, Department of Dermatology, New Haven, CT 06510-8059.
J Immunother (1991). 1992 Oct;12(3):154-61. doi: 10.1097/00002371-199210000-00002.
Normal human melanocyte proliferation and differentiation is dependent on stimulation of one of three growth factor/receptor systems. They are fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and mast cell growth factor (MGF), which activate the FGF receptor, c-Met, and c-Kit, respectively, known to be receptor tyrosine kinases. In contrast, human melanoma cells from primary nodular and metastatic lesions grow autonomously partially because of inappropriate production of basic FGF (bFGF) and continuous activation of the bFGF-receptor kinase. Activation of transmembrane receptor tyrosine kinases in melanocytes stimulates not only proliferation but also the expression of pigmentation. Melanoma cells constitutively express several tyrosyl-phosphorylated proteins that in normal melanocytes are stimulated in response to growth factors. This high level of phosphorylation was not due to either the presence of constitutively active Kit kinase and Met kinase nor to the absence of any of several known protein tyrosine phosphatases. Because bFGF by itself does not transform melanocytes to melanomas, there must be additional cooperating factors that confer the malignant phenotype to pigment cells.
正常人类黑素细胞的增殖和分化依赖于三种生长因子/受体系统之一的刺激。它们是成纤维细胞生长因子（FGF）、肝细胞生长因子（HGF）和肥大细胞生长因子（MGF），它们分别激活FGF受体、c-Met和c-Kit，这些已知为受体酪氨酸激酶。相比之下，来自原发性结节性和转移性病变的人类黑素瘤细胞部分由于碱性FGF（bFGF）的不适当产生和bFGF受体激酶的持续激活而自主生长。黑素细胞中跨膜受体酪氨酸激酶的激活不仅刺激增殖，还刺激色素沉着的表达。黑素瘤细胞组成性地表达几种酪氨酰磷酸化蛋白，在正常黑素细胞中这些蛋白是对生长因子作出反应而被刺激产生的。这种高水平的磷酸化既不是由于组成性活性Kit激酶和Met激酶的存在，也不是由于几种已知蛋白酪氨酸磷酸酶中任何一种的缺失。由于bFGF本身不会将黑素细胞转化为黑素瘤，所以必然存在其他协同因子赋予色素细胞恶性表型。
