Pathogenesis of multi-step progression of urothelial carcinoma and development of innovative treatment

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18612
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: The University of Tokushima
• Principal Investigator: DAIZUMOTO Kei 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (10745516)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 尿路上皮癌 / DDX31 / TP53 / p53 / 多段階進展

Outline of Final Research Achievements

The anti-tumor effect of DDX31 was verified in a preclinical model, and the amino acid sequence of the reciprocal site of DDX31 was identified to create a dominant negative peptide. We also examined the relationship between p53 and DDX31 in the uroepithelial carcinogenesis model using N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) as a uroepithelial carcinogenesis model. The results showed that DDX31 RNA expression was upregulated in the bladder tissue over time compared to the control group.

Free Research Field

尿路上皮癌

Academic Significance and Societal Importance of the Research Achievements

尿路上皮癌の遺伝子変異で大きく病態として分かれるのはTP53変異である。これまでの研究から尿路上皮癌・初期段階のTP53 wild type、中期段階のTP53 muation、後期段階のEGFRやHER2などReceptor of Tyrosine kinase (RTK)の活性化の病態解明にはまだ未解明な部分が多く、詳細に解析することで治療法の開発につながることが期待される。最終的に、尿路上皮癌の多段階進展機能のさらなる新機能発見と新規治療法の開発につながっていくことが期待される。