A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggest malignant progression

• Project/Area Number: 23592343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: KAWAGUCHI Makoto 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (50204699)
• Co-Investigator(Kenkyū-buntansha): MIURA Yutaka 名古屋市立大学, 大学院医学研究科, 准教授 (90285198)
• Project Period (FY): 2011-04-28 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: ATBF1 (ZFHX3) / 膀胱表在癌 / 核での局在 / 免疫組織科学 / Overall survival / ATBF1 / urothelial carcinoma / immunohistochemistry / malignant progression / 癌悪性度 / タンパク分断化 / 膀胱癌 / 免疫組織化学 / 神経発生 / 転写因子

Outline of Final Research Achievements

Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection. We are seeking a novel marker to distinguish high-risk cases to choose adequate treatment as soon as possible. A transcription factor, ATBF1 should be normally localized in the nucleus, but it has been observed in the cytoplasm of several cancers. When we distinguished two groups according to positive nuclear staining of ATBF1, we found a significant difference in overall survival and intravesical recurrence-free survival in ATBF1-positive compared with ATBF1-negative cases. Cleavage of ATBF1 increases cytoplasmic fragments of ATBF1 and reduces the amount of ATBF1 in the nucleus. Alteration of subcellular localization due to fragmentation of ATBF1 is related to the malignant character of urothelial carcinoma.

Research Products

• [Journal Article] ATBF1 is a novel amyloid-β protein precursor (AβPP) binding protein that affects AβPP expression. (2015)
  • Author(s): Uhm KO, Kim MJ, Kawaguchi M, Akatsu H, Miura Y, Misumi S, Hida H, Choi EK, Kim YS, Michikawa M, Jung CG
  • Journal Title: J Alzheimers Dis. Volume: 43(1) Pages: 243-57
  • Peer Reviewed
• [Presentation] 初回TUR膀胱癌細胞の、ATBF1細胞内局在変化により、膀胱癌 患者の全生存率、非再発生存率を予測出来る (2013)
  • Author(s): 川口誠、三浦裕
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌 キャッスル
• [Presentation] The ZFHX3 (ATBF1) Transcription Factor Induces PDGFRB, which Activates ATM in the Cytoplasm to Protect Cerebellar Neurons form Oxidative Stress (2012)
  • Author(s): Miura Y
  • Organizer: ATW 2012 14th International Workshop on Ataxia-teleangiectasia
  • Place of Presentation: Radisson Blu Hotel Paschem Vihar, （New Delhi, India）
• [Presentation] Fragmentation of ATBF1 shows distinct alteration of its subcellular localization suggesting malignancy of bladder cancer cells (2011)
  • Author(s): 川口誠
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Specific fragmentation at N-terminal of ATBF1 in adult brain (2011)
  • Author(s): Dong Yu
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] ATBF1 is highly phosphorylated in embryonic brain (2011)
  • Author(s): Zhang Sheng
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県）