Quantitative analysis of MEK inhibitor resistance in cancer cells based on reconstitution of cell growth signaling

2015 Fiscal Year Final Research Report

• Project/Area Number: 26890015
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Tumor biology
• Research Institution: Kyoto University
• Principal Investigator: Komatsu Naoki 京都大学, 生命科学研究科, 助教 (30737440)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: シグナル伝達 / 細胞増殖 / 生細胞イメージング

Outline of Final Research Achievements

The Ras-Raf-MEK-ERK signaling pathway plays pivotal roles in cell proliferation and cell growth and mutations in Ras or Raf have been frequently identified from various tumor cells. MEK inhibitors are effective in suppressing cell growth of Raf-mutant cells but not in Ras-mutant cells. To reveal working principles of the MEK inhibitor resistance in cancer cells, in this study, we constructed a system for controlling and monitoring mTORC1 activity, which is a downstream signaling of Ras. In addition, we established stable cell lines for analyzing dynamics of cell cycle progression of living tumor cells under perturbations of ERK or mTORC1 signaling. Combination of these approaches would be expected to identify the principles of cell growth control and that of MEK inhibitor resistance.

Free Research Field

細胞生物学