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Development of gene therapy for invasive bladder cancer focusing on genomic instability

Research Project

Project/Area Number 17K11154
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionNagoya City University

Principal Investigator

Yamada Kenji  名古屋市立大学, 医薬学総合研究院(医学), 研究員 (80566232)

Co-Investigator(Kenkyū-buntansha) 安井 孝周  名古屋市立大学, 医薬学総合研究院(医学), 教授 (40326153)
安藤 亮介  名古屋市立大学, 医薬学総合研究院(医学), 教授 (30381867)
内木 拓  名古屋市立大学, 医薬学総合研究院(医学), 講師 (50551272)
戸澤 啓一  名古屋市立大学, 医薬学総合研究院(医学), 教授 (40264733)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords膀胱癌 / UQCRB / 膀胱がん / 膀胱浸潤癌 / ゲノム不安定性 / 癌
Outline of Final Research Achievements

Genomic instability is the hallmark of most human cancers, including bladder cancer. However, its role in tumor carcinogenesis is still poorly understood. In this study, to investigate chromosomal instabilities (CIN), bladder cancer mouse model was used. As measure of CIN, DNA copy number aberrations (CNA) were investigated. According to array comparative genomic hybridization (CGH) analysis to detect CNA throughout the genome, five chromosomes with high CIN were identified, and among the candidate genes present in these regions, ubiquinol-cytochrome c reductase binding protein (UQCRB) on chromosome13B3 was further characterized. In this study, our findings suggest that UQCRB is an indicator of bladder cancer, and may play important roles in carcinogenesis through the regulation of iNOS.

Academic Significance and Societal Importance of the Research Achievements

膀胱の発がん進展過程は未だ不明な点が多い。近年、がんは遺伝子変化の集積に伴って多段階で生じ、染色体レベルでのゲノムの不安定性(Chromosomal instability:CIN)がみられることが解明されてきた。しかし、膀胱がん患者は遺伝・環境背景が多様でCINの解析は困難であった。このことから私は、膀胱がんモデルマウスを用いてCINを検討することにより、ヒト膀胱発がんに関わる遺伝子としてUQCRBを同定した。UQCRBはiNOSを介してヒト膀胱発がんの過程に関与しているものと考えられた。さらなる研究により発がんに関与するマーカーおよび治療法の開発の可能性があると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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