Development of novel therapy

我们筛选了人肾细胞癌细胞中界面泡状蛋白的表达水平和激活水平，发现癌细胞中一些蛋白相关的细胞内信号转导通路的激活加速。肝细胞生长因子/散射因子酪氨酸激酶受体MET蛋白在占人类肾癌80%左右的透明细胞肾癌中被组成性激活。人透明肾细胞癌易感性VHL基因失活诱导MET蛋白活化，我们发现手术获得的大多数透明肾细胞癌肿瘤组织中MET蛋白与正常组织相比出现了过度磷酸化。当MET抑制剂K252a抑制CCRC细胞中MET蛋白的激活时，CCRC细胞的体外生长和裸鼠体内CCRC细胞诱导的肿瘤发生均受到抑制。这些结果表明MET蛋白在人肾癌的肿瘤发生中起重要作用。同时，这些结果表明MET蛋白具有作为新型CCRC治疗的分子靶点的潜力。

We screened the expression levels and activation levels of intrace Ilular protein in human renal cell carcinoma cells and found that the activation of some protein associated intracellulax signal transduction pathways were accelerated in cancer cells. MET protein, the tyrosine kinase receptor for hepatocyte growth factor/scattering factor was constitutive activated in human clear cell renal carcinoma, which occupied about 80% of human kidney cancer. The activation of MET protein was induced by the inactivation of VHL gene which predisposed human clear renal cell carcinoma, we found that MET protein in most of clear renal cell carcinoma tumor tissues gained from surgeries showed hyperphosphorylation compared with that in normal tissues. When activation of MET protein in CCRC cells was inhibited by the MET inhibitor K252a, the growth of CCRC cells in vitro and the tumorigenesis induced by CCRC cells in nude mice were suppressed. From these results, we concluded that MET protein played important roles in tumorigenesis of human kidney cancer. At the same time, the results suggested that MET protein has a potential as a molecular target for novel CCRC therapies.