The involvement of sphingolipid metabolism in anti cancer drug sensitivity of malignant cells
| 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.
|
Report
(4 results)
Research Products
(21 results)
-
-
[Journal Article] Sphingosine kinase 1 expression is downregulated during differentiation of Friend cells due to decreased c-MYB.2013
Author(s)
Mizutani N, Kobayashi M, Sobue S, Ichihara M, Ito H, Tanaka K, Iwaki S,Fujii S,Ito Y, Tamiya-Koizumi K, Takagi A, Kojima T, Naoe T, Suzuki M, Nakamura M, Banno Y, Nozawa Y, Murate T.
-
Journal Title
Biochimica et Biophysica Acta -Molecular Cell Research
Volume: 1833
Issue: 5
Pages: 1006-16
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
[Presentation] The mechanism of cytotoxicity by resveratrol against human leukemia cell lines2013
Author(s)
Omori Y, Mizutani N, Inoue M, Nishida Y, Suzuki M, Koizumi K, Takagi A, Kojima T, Iwaki S, Fujii S, Nakamura M, Nozawa Y, Murate T
Organizer
7^<th> International Conference of Ceramide
Place of Presentation
Montauk, NY. USA
Year and Date
2013-10-22
Related Report
-
[Presentation] Regulatory mechanism of SPHK2 expresssion in colon cancer cell lines2013
Author(s)
Mizutani N, Inoue M, Nishida Y, Omori Y, Suzuki M, Koizumi K, Takagi A, Kojima T, Iwaki S, Fujii S, Nakamura M, Banno Y, Nozawa Y, Murate T
Organizer
7^<th> International Conference of Ceramide
Place of Presentation
Montauk, NY. USA
Year and Date
2013-10-21
Related Report
-
-
-
-
-
-
-
-
