| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Outline of Final Research Achievements |
This research project aimed to elucidate signaling and molecular mechanisms of (1) lung alveolarization, (2) skeletal muscle cell differentiation and regeneration, and (3) tumor suppression by the Ras-ERK pathway antagonist DA-Raf. We found that (1) suppression of the Ras-ERK pathway by DA-Raf is essential for TGF-β1-induced epithelial-mesenchymal transition from alveolar epithelial type 2 cells to myofibroblasts. (2) Suppression of the Ras-ERK pathway by DA-Raf is required for the induction of skeletal myocyte differentiation and apoptosis during myocyte differentiation. (3) The expression of DA-Raf was lost in tumor cells with constitutively active KRAS mutations. Inactivating mutations and SNP of DA-Raf did not suppress active K-Ras mutant-induced tumor phenotypes. Thus, DA-Raf represents a tumor suppressor protein against K-Ras-induced tumorigenesis.
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