Tumor microenvironment and ubiquitin system in platinum resistance urothelial carcinoma

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462429
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Keio University
• Principal Investigator: TANAKA NOBUYUKI 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (60445244)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 尿路上皮癌 / 上皮間葉転換 / シスプラチン / FBXO32 / 抗がん剤耐性

Outline of Final Research Achievements

To identify the molecules involved in epithelial-to-mesenchymal transition (EMT) in tumors post acquired platinum resistance (PR), we examined the changes in gene expression before and after platinum treatment. Four urothelial carcinoma cell lines, T24, 5637, and their PR sublines of T24PR and 5637PR, were assessed by microarray, and FBXO32 was newly identified as a negative regulator of EMT. In vitro study showed an intimate relationship between FBXO32 expression and EMT, demonstrating that FBXO32 knockdown resulted in the EMT acquisition. In contract, FBXO32 overexpression suppressed EMT. The association between FBXO32 expression and EMT was further validated using human specimens. CGH array analysis demonstrated loss of heterozygosity at 8q24.13 in T24PR cells, which harbors FBXO32. In 5637PR cells, decreased nuclear FOXO1/3a expression seemed to affect FBXO32 dysregulation. These results suggest the association between EMT and ubiquitin-proteasome regulation when tumors develop PR.

Free Research Field

泌尿器科学