Analyses of altered VHL protein function in the clear cell renal carcinoma(CRCC) and its utilization for CRCC patients.

透明细胞肾细胞癌（CCRCC）是肾癌中最常见的病理类型之一。VHL基因突变导致HIF1a和HIF2a蛋白的积累。HIF蛋白的积累导致VEGF蛋白的表达增加。目前许多靶向VEGF受体的分子药物是治疗转移性肾癌最常用的药物之一。然而，应该注意的是，一些突变的VHL蛋白具有残余的正常功能或改变了其他功能。为了阐明突变蛋白的残留或功能改变，我们将CCRCC中检测到的突变VHL基因引入到VHL双敲除小鼠胚胎成纤维细胞（MEFs）中，我们可以发育MEF1和MEF2。只有一个突变的VHL蛋白导致HIF1a的功能下降。其他突变的VHL蛋白不会导致类似的变化。为了了解CCRCC及其治疗方案，我们希望进一步分析突变VHL蛋白的功能改变。

Clear cell renal cell carcinoma (CCRCC) is one of the most common pathological type in kidney cancer. VHL gene mutation results in the accumulation of HIF1a and HIF2a protein. Accumulation of HIF protein results in the increased expression of VEGF proteins. Currently many molecular targeting drugs for VEGF receptor are one of the most popular treatments for metastatic kidney cancers. However, it should be noted that some of mutant VHL protein has a residual normal function or altered other function.To elucidate the residual or altered function in the mutant protein we introduced mutant VHL gene detected in CCRCC to VHL double knockout mouse embryonal fibroblasts(MEFs), and we could develop MEF1 and MEF2. Only one mutant VHL protein resulted in the decreased function in HIF1a. Other mutant VHL protein could not result in the similar changes. To understand CCRCC and its treatment option, we would like to analyze altered function in mutant VHL proteins further.