Molecular function of BMCC1 in favorable prognosis of neuroblastoma

• Project/Area Number: 26461602
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Tatsumi Yasutoshi 千葉県がんセンター(研究所), がん予防センター 腫瘍ゲノム研究室, 研究員 (00450578)
• Co-Investigator(Kenkyū-buntansha): 中川原 章 千葉県がんセンター(研究所), その他部局等, その他 (50117181)
• Research Collaborator: Islam Mohammad Sazzadul 千葉大学, 大学院、医学研究院
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 神経芽腫 / アポトーシス / 抗癌剤耐性 / DNA損傷応答 / 細胞周期 / 自然退縮 / DNA損傷 / BMCC1 / E2F1 / 転写制御 / 細胞死 / 細胞死促進因子

Outline of Final Research Achievements

In this study, first, we found transcriptional regulation of BMCC1 mediated by E2F1 in neuroblastoma cells. Then, we clarified a functional role of BMCC1 in apoptosis promotion of neuroblastoma cells. Furthermore, we found that reduced expression of BMCC1 may become malignant neuroblastoma by abrogating DNA damage repair and apoptosis. Molecular functions of BMCC1 uncovered in this study provide clues for defining the underlying molecular mechanism(s) that determine whether the course of neuroblastoma will be favorable or unfavorable. These results were presented at several academic conferences and also reported as academic papers (Tatsumi et al., CDDIS, 2015; Islam and Tatsumi et al., BBRC, 2016).

Research Products

• [Journal Article] Transcriptional regulation of BMCC1 mediated by E2F1 in neuroblastoma cells (2016)
  • Author(s): Mohammad Sazzadul Islam, Yasutoshi Tatsumi, Ryo Takano, Tomoki Yokochi, Jesmin Akter, Toshinori Ozaki, Yohko Nakamura, Miki Ohira, and Akira Nakagawara
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 478 Issue: 1 Pages: 81-86
  • DOI: 10.1016/j.bbrc.2016.07.089
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] BMCC1, which is an interacting partner of BCL2, attenuates AKT activity, accompanied by apoptosis. (2015)
  • Author(s): Tatsumi Y, Takano R, Islam MS, Yokochi T, Itami M, Nakamura Y, Nakagawara A.
  • Journal Title: Cell Death Dis. Volume: 6 Issue: 1 Pages: e1607-e1607
  • DOI: 10.1038/cddis.2014.568
  • Peer Reviewed / Open Access
• [Presentation] 難治性神経芽腫の網羅的ゲノム・エピゲノムプロファイル (2016)
  • Author(s): 大平 美紀、巽 康年、中村 洋子、辰野 健二、堤 修一、山本 尚吾、永江 玄太、Claire Renard-Guillet、杉野隆一、永瀬 浩喜、上條 岳彦、油谷 浩幸、中川原 章
  • Organizer: 第75回日本癌学会学術集会
  • Place of Presentation: 神奈川県・横浜市・パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] BMCC1, a tumor suppressor protein that facilitates DNA-damage response and apoptosis, is associated with favorable prognosis of neuroblastoma (2016)
  • Author(s): Yasutoshi Tatsumi, Mohammad Sazzadul Islam, MIki Ohira, Yohko Nakamura and Akira Nakagawara
  • Organizer: Advances in Neuroblastoma Research Congress 2016
  • Place of Presentation: オーストラリア・ケアンズ市
  • Year and Date: 2016-06-20
  • Int'l Joint Research
• [Presentation] BMCC1, a tumor suppressor protein that facilitates DNA-damage response and apoptosis, is associated with favorable prognosis of neuroblastoma (2016)
  • Author(s): Y Tatsumi, MS Islam, M Ohira, Y Nakamura and A Nakagawara
  • Organizer: ANR 2016
  • Place of Presentation: オーストラリア・ケアンズ市・Cairns Convention Center
  • Year and Date: 2016-06-19
  • Int'l Joint Research
• [Presentation] Clinical relevance of genomic and epigenomic classification of MYCN-non-amplified neuroblastoma (2016)
  • Author(s): M Ohira, Y Nakamura, Y Tatsumi, K Tatsuno, S Tsutsumi, S Yamamoto, G Nagae, C Renard-Guillet, R Sugino, M Haruta, H Takenobu, H Nagase, T Kamijo, H Aburatani, A Nakagawara
  • Organizer: ANR 2016
  • Place of Presentation: オーストラリア・ケアンズ市・Cairns Convention Center
  • Year and Date: 2016-06-19
  • Int'l Joint Research
• [Presentation] E2F1 induces expression of BMCC1 and facilitates phosphorylation of ATM in neuroblastoma (2015)
  • Author(s): Yasutoshi Tatsumi, Mohammad Sazzadul Islam, Yohko Nakamura, Miki Ohira, Akira Nakagawara
  • Organizer: 第３８回分子生物学会年会 第８８回日本生化学会大会 合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-03
• [Presentation] Genomic profiling of intermediate risk type of neuroblastoma without MYCN amplification (2015)
  • Author(s): M.Ohira, Y.Nakamura, K.Tatsuno, S.Tsutsumi, S.Yamamoto, G.Nagae, Y.Tatsumi, H.Nagase, T.Kamijo, H.Aburatani, A.Nakagawara
  • Organizer: 第57回日本小児血液・がん学会学術集会
  • Place of Presentation: 甲府市
  • Year and Date: 2015-11-27
• [Presentation] Genomic characterization of aggressive subtypes of neuroblastoma with 11q partial loss (2015)
  • Author(s): M.Ohira, Y.Nakamura, K.Tatsuno, S.Tsutsumi, S.Yamamoto, G.Nagae, Y.Tatsumi, H.Nagase, T.Kamijo, H.Aburatani, A.Nakagawara,
  • Organizer: 神経芽腫アジアパシフィックシンポジウム2015
  • Place of Presentation: 台湾・台北市
  • Year and Date: 2015-11-14
  • Int'l Joint Research
• [Presentation] whole exome sequencing による小児骨肉腫肺転移関連体細胞変異の検索 (2015)
  • Author(s): 巽康年, 岩田慎太郎, 米本司, 鴨田博人, 石井猛, 永瀬浩喜, 大平美紀
  • Organizer: 第74回日本癌学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-10-10
• [Presentation] 半導体次世代シークエンサーによるリスク集団特異的がん関連遺伝子多型解析 (2015)
  • Author(s): 中村洋子, 丸喜明, 巽康年, 横井左奈, 大平美紀, 中村友紀, 高山喜美子, 稲田潤子, 田中尚武, 山本尚人, 鍋谷圭宏, 滝口伸浩, 植田健, 片山稔, 永瀬浩喜, 三上春夫
  • Organizer: 第74回日本癌学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-10-10
• [Presentation] 1q欠失を伴った難治性中間リスク型神経芽腫のゲノム・エピゲノム解析 (2015)
  • Author(s): 大平美紀, 中村洋子, 辰野健二, 堤修一, 山本尚吾, 永江玄太, 巽康年, 永瀬浩喜, 上條岳彦, 油谷浩幸, 中川原章
  • Organizer: 第74回日本癌学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-10-10
• [Presentation] BMCC1, an independent favorable marker of neuroblastoma, facilitates ATM phosphorylation after transcription by E2F1. (2015)
  • Author(s): Mohammad Sazzadul Islam, Yasutoshi Tatsumi, Jesmin Akter, Miki Ohira, Akira Nakagawara
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-10-08
• [Presentation] 半導体次世代シーケンサーを用いたがん臨床検体のゲノムシーケンシング (2014)
  • Author(s): 巽 康年、丸 喜明、中村友紀、大平美紀、伊丹真紀子、片山 稔、横井左奈、永瀬浩喜
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: 神奈川県・横浜市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] BMCC1, a multifunctional scaffold protein, promotes mitochondrial apoptosis and attenuates AKT survival signal after E2F1-dependent induction in neuroblastoma (2014)
  • Author(s): Yasutoshi Tatsumi, Mohammad Sazzadul Islam, Ryo Takano, Yohoko Nakamura and Akira Nakagawara
  • Organizer: ADVANSES IN NEUROBLASTOMA RESEARCH Congress・2014
  • Place of Presentation: ドイツ・ケルン市
  • Year and Date: 2014-05-13 – 2014-05-16
• [Presentation] BMCC1, a pro-apoptotic gene upregulated by E2F1 after DNA damage, facilitates the drug sensitivity of neuroblastoma cells (2014)
  • Author(s): Mohammad Sazzadul Islam, Yasutoshi Tatsumi, Ryo Takano, Jesmin Akter and Akira Nakagawara
  • Organizer: ADVANSES IN NEUROBLASTOMA RESEARCH Congress・2014
  • Place of Presentation: ドイツ・ケルン市
  • Year and Date: 2014-05-13 – 2014-05-16