| Project/Area Number |
21791378
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
MUTOH Jun Keio University, 医学部, 助教 (30383839)
|
|---|
| Project Period (FY) |
2009 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 癌 / 遺伝子 / 脳疾患 / 悪性神経膠芽腫 / 腫瘍幹細胞 / Musashi1 / 細胞増殖 / 脳腫瘍 / 癌幹細胞 / Musashil |
|---|
| Research Abstract |
The expression of Musashi1 (MSI1), an RNA-binding protein that plays a crucial role in nervous system development and stem cell self-renewal. Here, we examined its role in the progression of glioma. The RNAi-based MSI1-knock down (KD) in glioblastoma and medulloblastoma cells resulted in a significantly lower number of colony forming cells on day 30 (66% reduction in colony size), indicative of the inhibitory effect of MSI1-KD on tumor cell growth. Immunocytochemical staining of MSI1-KD glioblastoma cells suggested that these cells ectopically express markers of Meta-phase. A 2.2 -fold increased number of MSI1-KD cells in the G2/M phase, as detected by fluorescence cell sorting, further confirmed the induction of mitosis and defect of cell survival upon MSI1-KD treatment, although it did not alter the expression of, activated caspase-3. We further showed that the xenografts of MSI1-KD glioblastoma cells had a 96.6% reduction of tumor size measured by bioluminescence imaging system(BLI) and longer survival (49.3±6.1 days) than the control group (33.6±3.6 days ; P<0.01). Taken together, these findings and gene analysis suggest that in MSI1-KD in glioma cells results in the prolongation of the cell cycle by accumulating cyclin B and reduced activity of Notch signal pathway accompanying with up-regulation of m-Numb, which could cause the decrease of survival of glioma cells..
|
