Zakut R, Perlis R, Eliyahu S, Yarden Y, Givol D, Lyman S D, Halaban R
National Cancer Institute, Surgery Branch, Bethesda, Maryland 20892.
Oncogene. 1993 Aug;8(8):2221-9.
Previous studies in vivo and in vitro show that KIT kinase promotes normal melanocyte development and growth. However, the role of the KIT proto-oncogene in neoplastic melanocytes is not certain. We therefore examined KIT expression and function in human melanomas. Our results show that KIT mRNA was expressed in 12 of 28 melanoma cell lines (approximately 40%), mainly in those originating from pigmented tumors. Surprisingly, activation of KIT with mast cell growth factor (MGF) in melanoma cells produced biological responses opposite to those elicited in normal melanocytes. MGF inhibited rather than stimulated the growth of metastatic melanoma cell lines. The opposite effects may be due to aberrant signal transduction by KIT in melanoma cells in response to MGF. The in vitro inhibition of melanoma cells by MGF suggests that growth in vivo of this tumor is not promoted by KIT kinase activation, but rather that transformed melanocytes might regress when MGF is expressed in their immediate environment.
先前的体内和体外研究表明，KIT激酶可促进正常黑素细胞的发育和生长。然而，KIT原癌基因在黑素瘤细胞中的作用尚不确定。因此，我们检测了KIT在人类黑色素瘤中的表达和功能。我们的结果显示，28个黑色素瘤细胞系中有12个表达KIT mRNA（约40%），主要是那些起源于色素性肿瘤的细胞系。令人惊讶的是，在黑色素瘤细胞中用肥大细胞生长因子（MGF）激活KIT产生的生物学反应与在正常黑素细胞中引发的反应相反。MGF抑制而非刺激转移性黑色素瘤细胞系的生长。这种相反的作用可能是由于黑色素瘤细胞中KIT对MGF的信号转导异常。MGF对黑色素瘤细胞的体外抑制表明，该肿瘤在体内的生长并非由KIT激酶激活所促进，而是当MGF在其周围环境中表达时，转化的黑素细胞可能会消退。
