Identification of taxane-binding protein by utilizing magnetic beads to clarify the molecular mechanism how to develop taxane-resistance in prostate cancer

• Project/Area Number: 24592405
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: TAKAHA Natuski 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (80294081)
• Co-Investigator(Kenkyū-buntansha): MIKI Tsuneharu 京都府立医科大学, 医学研究科, 教授 (10243239) ; KAWAUCHI Akihiro 滋賀医科大学, 医学部, 教授 (90240952) ; KAMOI Kazumi 京都府立医科大学, 医学研究科, 講師 (40295663) ; OKIHARA Koji 京都府立医科大学, 医学研究科, 准教授 (80285270) ; KIMURA Yasunori 京都府立医科大学, 医学研究科, 助教 (20398374) ; UEDA Takashi 京都府立医科大学, 医学研究科, 助教 (50601598) ; IWATA Tsuyoshi 京都府立医科大学, 医学研究科, 客員講師 (00552209) ; OISHI Masakatsu 京都府立医科大学, 医学研究科, 助教 (90405316) ; UEDA Saya (ITO Saya) 京都府立医科大学, 医学研究科, 助教 (90534511)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 前立腺癌 / 抗癌剤耐性 / タキサン / ナノビーズ / ケミカルバイオロジー

Outline of Final Research Achievements

We identified tubulin, coatomer protein complex subunit alpha, and basonuclin-1 as docetaxel-binding protein overexpressed in docetaxel-resistant subcell line established from prostate cancer cell line DU145 by utilizing magnetic beads. The relative RNA expression level (docetaxel resistant/sensitive) of those molecules was about 70%, 100%, and 20%, respectively. As tubulin, which is a target molecule for docetaxel was identified, the applied method should be appropriate as purifying docetaxel-binding protein. However, the expression profile of RNA and that of protein did not coincide, which made it difficult to judge the role of the identified docetaxel-binding protein in the development of docetaxel-resistance.

Research Products

• [Presentation] HIGH MOBILITY GROUP PROTEIN AT-HOOK 1 (HMGA1) IS ASSOCIATED WITH THE DEVELOPMENT OF ANDROGEN INDEPENDENCE AND DOCETAXEL-RESISTANCE IN PROSTATE CANCER CELLS
  • Author(s): Natsuki Takaha, Yoshihiro Sowa, Ichiro Takeuchi, Takashi Ueda, Saya Ito-Ueda, Yasunori Kimura, Tsuyoshi Iwata, Terukazu Nakamura, Fumiya Hongo, Kazumi Kamoi, Koji Okihara, Akihiro Kawauchi, Tsuneharu Miki
  • Organizer: 108th American Urological Association Annual Meeting
  • Place of Presentation: San Diego Convention Center
• [Presentation] 前立腺癌細胞のアンドロゲン非依存性増殖およびドセタキセル抵抗性獲得におけるhigh mobility group protein AT-hook 1(HMGA1)の役割
  • Author(s): 高羽 夏樹、曽和 義広、竹内 一郎、上田 崇、木村 泰典、岩田 健、中村 晃和、本郷 文弥、三神 一哉、鴨井 和実、沖原 宏治、河内 明宏、三木 恒治
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜
• [Presentation] 前立腺癌細胞におけるアンドロゲン非依存性細胞生存とドセタキセル抵抗性に関するHMGA1の関連
  • Author(s): 高羽 夏樹、曽和 義広、竹内 一郎、上田 崇、木村 泰典、岩田 健、中村 晃和、本郷 文弥、 鴨井 和実、沖原 宏治、河内 明宏、 三木 恒治
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌