| Project/Area Number |
23590667
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory medicine
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
MURATE Takashi 名古屋大学, 医学(系)研究科(研究院), 教授 (30239537)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KIJIMA Tetsuhito 名古屋大学, 大学院医学系研究科, 教授 (40161913)
TAKAGI Akira 名古屋大学, 大学院医学系研究科, 助教 (30135371)
SUZUKI Motoshi 名古屋大学, 大学院医学系研究科, 講師 (80236017)
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
|---|
| Keywords | sphingolipid / metabolic enzyme / gene expression / anti-cancer drug / human cancer cell lines / SPHK1 / Friend cell / c-Myb / chemical differentiation / human colon cancer cell / CD44 / S1P receptor 2 / ERK pathway / 国際情報交換 / NSmase2 / ATRA / MCF-7細胞株 / プロモーター解析 / Sp1転写因子 / PKC delta |
|---|
| Research Abstract |
In the first year, we analyzed the mechanism of GAP43 expression during GDNF treatment of a neuronal cel line, TGW. Our analysis revealed that GDNF induced SPHK1 expression through RET receptor, followed by S1P secretion and S1P1/3 receptor activation. We further found that GAP43 expression was due to the increased CREB transcription factor binding to the GAP43 5'-promoter region.
Next, we analyzed the regulatory mechanism of neutral sphingomyelinase 2 and neutral ceramidase with all trans retinoid acid (ATRA). Our analysis revealed that activated Sp1 transcription factor and decreased GATA2 were responsive for the observed changes in treated MCF-7 and SH-SY5Y cells, respectively.
In the third year, we analyzed the mechanism of high SPHK1 expression of mouse Friend cells. We found that c-MYB is responsible for this overepression and that chemical inducer, HMBA, rapidly decreased SPHK1 expression, which is at least partially responsible for this terminal differentiation process.
|
