Development of novel therapy

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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.