Clarification of the multistage carcinogenesis and basis of the innovative therapeutics for Renal Cell Carcinoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04975
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Kumamoto University
• Principal Investigator: Baba Masaya 熊本大学, 国際先端医学研究機構, 准教授 (10347304)
• Co-Investigator(Kenkyū-buntansha): 江藤 正俊 九州大学, 大学病院, 教授 (90315078) ; 矢尾 正祐 横浜市立大学, 医学研究科, 教授 (00260787) ; 長嶋 洋治 東京女子医科大学, 医学部, 教授 (10217995) ; 古屋 充子 横浜市立大学, 医学部, 准教授 (10361445)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 腎細胞癌 / がん抑制遺伝子 / Birt-Hogg-Dube症候群 / 転座型腎細胞癌

Outline of Final Research Achievements

In this study, we focused on two kinds of renal cell carcinoma (RCC), BHD associated RCC whose responsible gene is a tumor suppressor FLCN, and Xp11.2 translocation RCC (tRCC) that expresses chimeric TFE3 produced by Xp11.2 translocation. We utilized genetically engineered mice, human RCC tissues and cell lines to study molecular mechanisms for RCC development, identify driver gene mutations, and develop new diagnostic markers or therapeutics for RCC. We clarified that FLCN altered intracellular signaling through the regulation of cellular metabolism. We then demonstrated that chromatin remodeling genes were frequently mutated in BHD associated RCC. We also demonstrated that chimeric TFE3 proteins worked as oncogenic transcription factors by acquiring altered functions. Finally, we identified a diagnostic marker for tRCC and confirmed its efficacy using human tRCC samples.

Free Research Field

泌尿器科学