Hypoxia resistance of cancer cells by suppressing IGF/PI3K/mTOR

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
• Principal Investigator: INOUE Masahiro Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses, 総括研究員 (10342990)
• Co-Investigator(Kenkyū-buntansha): ENDO Hiroko 地方独立行政法人大阪府立病院機構, 大阪府立成人病センター研究所, 研究員 (20359300)
• Project Period (FY): 2007 – 2008
• Keywords: 分子腫瘍学 / IGF / PI3K / mTOR / 低酸素 / 細胞死

Research Abstract

従来の癌研究は増殖に代表される活動型の癌細胞を対象としてきたが、環境に応じて活動を抑制して潜在型に移行できる癌細胞の性質に着目した研究はほとんど行われていない。本研究では増殖シグナルが環境に応じてON/OFF 切替えされる機構の重要性を検討した。つまり、低酸素下で抑制される増殖シグナルが持続することは癌細胞の生存に不利であり、癌細胞は環境に応じて増殖シグナルを抑制する仕組みを備えていることを明らかにした。

Research Products

• [Journal Article] Insulin-like growth factor stimulation increases radiosensitivity of a pancreatic cancer cell line through ER stress under hypoxic conditions (2008)
  • Author(s): Isohashi, F., Endo, H., Mukai, M., Inoue, T., Inoue, M.
  • Journal Title: Cancer Sci 99 Pages: 2395-2401
  • Peer Reviewed
• [Journal Article] IGFBPs contribute to survival of pancreatic cancer cells under severely hypoxic conditions (2008)
  • Author(s): Koga, T., Endo, H., Miyamoto, Y., Mukai, M., Akira, S., Inoue, M.
  • Journal Title: Cancer Lett 68 Pages: 62-88
  • Peer Reviewed
• [Journal Article] mTOR 経路と小胞体ストレス (2008)
  • Author(s): 井上正宏
  • Journal Title: 生体の科学(医学書院) 59 Pages: 516-521
• [Journal Article] Activation of insulin-like growth factor signaling induces apoptotic cell death under prolonged hypoxia by enhancing endoplasmic reticulum stress response (2007)
  • Author(s): Endo, H., Murata, K., Mukai, M., Ishikawa, O., Inoue, M.
  • Journal Title: Cancer Res 67 Pages: 8095-8103
  • Peer Reviewed
• [Journal Article] Significance of HIF-1-active cells in angiogenesis and radioresistance (2007)
  • Author(s): Harada, H., Kizaka-Kondoh, S., Li, G., Itasaka, S., Shibuya, K., Inoue, M., Hiraoka, M.
  • Journal Title: Oncogene 26 Pages: 7508-7516
  • Peer Reviewed
• [Journal Article] Regulation of hypoxia-inducible factor 1 by glucose availability under hypoxic conditions (2007)
  • Author(s): Zhou, J., Hara, K., Inoue, M., Hamada, S., Yasuda, H., Moriyama, H., Endo, H., et al.
  • Journal Title: Kobe J Med Sci 53 Pages: 283-296
  • Peer Reviewed
• [Journal Article] 癌と低酸素 (2007)
  • Author(s): 井上正宏
  • Journal Title: 実験医学(羊土社) 25 Pages: 2114-2119
• [Journal Article] 癌の低酸素応答 (2007)
  • Author(s): 井上正宏
  • Journal Title: 実験医学(羊土社) 25 Pages: 2132-2138
• [Presentation] Tumor dormancy in hypoxia (2008)
  • Author(s): Inoue M.
  • Organizer: STARGET workshop
  • Place of Presentation: Stockholm, Sw
  • Year and Date: 20081017-19
• [Presentation] Down-regulation of metabolism in cancer cells is an adaptive response to hypoxic conditions (2007)
  • Author(s): 井上正宏, 遠藤洋子
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04