Easty D J, Herlyn M, Bennett D C
St. George's Hospital Medical School, London, UK.
Int J Cancer. 1995 Jan 3;60(1):129-36. doi: 10.1002/ijc.2910600119.
Protein tyrosine kinases have been implicated in tumor initiation and progression. Here we used Northern blotting to study expression of their genes in cultured normal melanocytes and 19 melanoma cell lines from different stages of tumor progression. We detected transcripts for 2 cytoplasmic (ABL and FES) and 6 receptor (ECK, ERB-B2, FGF-R4, IGFI-R, KDR and TIE) kinases but not for receptors RET or TRK-A. Genes for ECK, FGF-R4 and TIE were expressed ectopically in melanomas (not in normal melanocytes). Similarly, ECK protein was detected by immunoblotting in metastatic melanomas but not in normal melanocytes. ECK mRNA levels tended to increase again during late melanoma progression. ECK and TIE mRNAs were also detected in highly metastatic variant cells but not in the corresponding poorly metastatic parental lines. Conversely, FES and KDR gene expression was lost in most advanced primary and metastatic melanomas. These findings suggest positive and negative roles for specific tyrosine kinases during progression.
蛋白酪氨酸激酶与肿瘤的发生和发展有关。在此，我们运用Northern印迹法研究了它们的基因在培养的正常黑素细胞以及来自肿瘤发展不同阶段的19种黑色素瘤细胞系中的表达情况。我们检测到了2种胞质激酶（ABL和FES）以及6种受体激酶（ECK、ERB - B2、FGF - R4、IGFI - R、KDR和TIE）的转录本，但未检测到受体RET或TRK - A的转录本。ECK、FGF - R4和TIE的基因在黑色素瘤中异位表达（正常黑素细胞中不表达）。同样，通过免疫印迹在转移性黑色素瘤中检测到了ECK蛋白，但在正常黑素细胞中未检测到。在黑色素瘤进展后期，ECK mRNA水平倾向于再次升高。在高转移性变异细胞中也检测到了ECK和TIE mRNA，但在相应的低转移性亲代细胞系中未检测到。相反，在大多数晚期原发性和转移性黑色素瘤中，FES和KDR基因表达缺失。这些发现表明特定酪氨酸激酶在肿瘤进展过程中具有正向和负向作用。
