Function of Insulin-like growth factor in neuroblastoma cell proliferation

• Project/Area Number: 25461590
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Mie University
• Principal Investigator: Komada Yoshihiro 三重大学, 学内共同利用施設等, 学長 (80186791)
• Co-Investigator(Kenkyū-buntansha): Toyoda Hidemi 三重大学, 医学(系)研究科(研究院), 助教 (60525327)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経芽腫 / インスリン様成長因子 / 細胞内増殖シグナル / インスリン様増殖因子 / 細胞増殖 / PDK1-mTOR経路 / AKT阻害剤 / mTOR阻害剤 / インスリン / アポトーシス細胞死 / オートクライン機構 / 細胞回転 / インスリン様増殖因子受容体 / インスリン受容体

Outline of Final Research Achievements

Insulin-like growth factor receptor (IGF-R) plays an important role on cancer cell proliferation.
It has been shown that neuroblastoma (NB) cells can be categorized into three groups by the patterns of IGF-R pathway response. The IGF-R pathway can be activated by endogenous IGF in group 1 NB cells. Stimulation of IGF-R pathway can be induced by exogenous IGF in group 2 NB cells. Activated IGF-R pathway hardly accelerate the cell proliferation of group 3 NB cells. In addition, IGF-R growth stimulation can be mediated by several different intracellular signal transduction pathways.
These results suggest that the significant heterogeneity of NB cells in IFG-R-mediated cell proliferation response should be taken enough into consideration, when any signal transduction inhibitors are used in the clinical treatment of NB patients.

Research Products

• [Journal Article] PDK1-mTor signaling pathway inhibitors reduce cell proliferation in MK2206 resistant neuroblastoma cells (2015)
  • Author(s): Lei Qi, Hidemi Toyoda, Dong-qing Xu, Ye Zhou, Naoto Sakurai, Keishirou Amano, Kentaro Kihira, Hiroki Hori, Eiichi Azuma, Yoshihiro Komada
  • Journal Title: Cancer Cell International Volume: 15 Issue: 1 Pages: 91-104
  • DOI: 10.1186/s12935-015-0239-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Heterogeneity of neuroblastoma cell lines in insulin-like growth factor 1 receptor/Akt pathway-mediated cell proliferative responses. (2013)
  • Author(s): Qi L, Toyoda H, Shankar V, Sakurai N, Amano K, Kihira K, Iwasa T, Deguchi T, Hori H, Azuma E, Gabazza EC, Komada Y
  • Journal Title: Cancer Science Volume: 104 Issue: 9 Pages: 1162-1171
  • DOI: 10.1111/cas.12204
  • Peer Reviewed