Molecular mechanisms of tissue formation, regeneration, and tumor suppression by the Ras-ERK pathway antagonist DA-Raf
| Project/Area Number |
15H04348
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
ENDO Takeshi 千葉大学, 大学院理学研究院, 教授 (30194038)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
TAKANO Kazunori 千葉大学, 大学院理学研究院, 助教 (60466860)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| 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)
|
|---|
| Keywords | Ras-ERK経路 / 肺胞形成 / 筋細胞分化 / 筋再生 / がん抑制 / 分子機構 / 組織形成 / 再生 |
|---|
| 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.
|
Report
(4 results)
Research Products
(21 results)
