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

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592334
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kochi University
• Principal Investigator: SHUIN TARO 高知大学, 教育研究部医療学系, 教授 (70128601)
• Co-Investigator(Renkei-kenkyūsha): KARASHIMA Takashi 高知大学, 教育研究部医療学系, 助教 (60304672) ; ASHIDA Shingo 高知大学, 教育研究部医療学系, 助教 (80380327) ; TAMURA Kenji 高知大学, 教育研究部医療学系, 助教 (50464384) ; SOGAWA Kazuhiro 東北大学, 生命科学研究科, 教授 (80175421) ; KAKINUMA Yoshihiko 日本医科大学, 大学院医学研究科, 大学院教授 (40233944)
• Project Period (FY): 2011 – 2013
• Keywords: VHL遺伝子変異 / HIF1α / HIF2α / ES細胞

Research Abstract

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.