Development of new animal model of invasive bladder cancer based on new generation OMICS analysis between species

• Project/Area Number: 25713055
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Urology
• Research Institution: Kyoto University
• Principal Investigator: Kobayashi Takashi 京都大学, 医学(系)研究科(研究院), 助教 (00642406)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000); Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
• Keywords: 膀胱癌 / 動物モデル / 発癌 / マウス発癌モデル / lineage tracing / 全エクソームシークエンス / 全エクソームシーケンス

Outline of Final Research Achievements

Upon administration of 0.1% BBN for 20 weeks after inducing two types of TP53 point mutations (R172H, R270H) in the urothelial cells expressing Krt5 or Upk2 by using the lox - stop - lox system, bladder cancer tissues originating from those mutant cells were obtained. Mouse bladder cancer tissues of each lineage were compared by pathological evaluation and expression microarray, and as a result, when TP 53 point mutation was induced in Krt5 expressing cells, muscle invasive bladder cancer with squamous differentiation, similar to human bladder cancer belonging to TCGA cluster 3, was generated most efficiently.