The functional role of chromatin remodeling regualtor Brg1 in pancreatic cancer

• Project/Area Number: 25461021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: Fukuda Akihisa 京都大学, 医学(系)研究科(研究院), 助教 (70644897)
• Co-Investigator(Renkei-kenkyūsha): SENO HIROSHI 京都大学, 医学研究科, 教授 (90335266)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 膵癌 / マウスモデル / 膵臓がん / IPMN / クロマチンリモデリング / 膵臓癌

Outline of Final Research Achievements

Pancreatic ductal adenocarcinoma (PDA) develops through distinct precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). However, little is known about molecular mechanisms of development of IPMN and IPMN-derived PDA. We have recently reported that loss of Brg1, a core subunit of SWI/SNF chromatin remodeling complexes, cooperates with oncogenic Kras to form cystic neoplastic lesions that resemble human IPMN and progress to PDA. We revealed that Brg1 is a determinant of context-dependent Kras-driven pancreatic tumorigenesis and chromatin remodeling may underlie the development of distinct PDA subsets.

Research Products

• [Journal Article] Molecular Mechanism of Intraductal Papillary Mucinous Neoplasm (IPMN) and IPMN-derived Pancreatic Ductal Adenocarcinoma (2015)
  • Author(s): Fukuda A
  • Journal Title: J Hepatobiliary Pancreatic Sci Volume: ２２ Pages: 519-23
  • Peer Reviewed
• [Journal Article] Molecular mechanism of Intraductal Papillary Mucinous Neoplasm (IPMN) and IPMN-derived Pancreatic Ductal Adenocarcinoma. (2015)
  • Author(s): Fukuda, A
  • Journal Title: J Hepatobiliary Pancreatic Sci Volume: in press
  • Peer Reviewed
• [Journal Article] The Chromatin Regulator Brg1 Suppresses Formation of Intraductal Papillary Mucinous Neoplasm and Pancreatic Ductal Adenocarcinoma. (2014)
  • Author(s): von Figura G*, Fukuda A*, Roy N* Roy N*, Liku ME, Morris Iv JP, Kim GE, Russ HA, Firpo MA, Mulvihill SJ, Dawson DW, Ferrer J,Mueller WF, Busch A, Hertel KJ, Hebrok M. co-first authors
  • Journal Title: Nature Cell Biology Volume: 16 Issue: 3 Pages: 255-267
  • DOI: 10.1038/ncb2916
  • Peer Reviewed
• [Journal Article] Brg1はIPMNおよびIPMN由来膵癌の形成を抑制する (2014)
  • Author(s): 福田晃久
  • Journal Title: 分子消化器病 Volume: 12
• [Presentation] クロマチンリモデリング因子Ｂrg１はIＰＭＮおよびIPMN由来膵癌の発生を抑制する (2016)
  • Author(s): Fukuda A, Chiba T, Seno H
  • Organizer: 第20回分子標的治療学会学術集会
  • Place of Presentation: 別府
  • Year and Date: 2016-05-31
  • Invited
• [Presentation] Identification of a pancreatic tumor specific stem cell marker. (2014)
  • Author(s): Takahisa Maruno, Akihisa Fukuda, Hiroshi Seno, Tsutomu Chiba.
  • Organizer: 第73回日本癌学会学術総会 2014 東京.
  • Place of Presentation: 東京
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 膵臓癌の発生におけるクロマチンリモデリング因子Brg1の役割
  • Author(s): Fukuda A*, von Figura G*, Roy N*, Liku ME, Morris Iv JP, Kim GE, Russ HA, Firpo MA, Mulvihill SJ, Dawson DW, Ferrer J, Mueller WF, Busch A, Hertel KJ, Hebrok M. * Equal Atuthorship
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートピアホテル（神戸)
  • Invited