| RRC ID |
43204
|
| 著者 |
Ishihara K, Kitamura H, Hiraizumi K, Kaneko M, Takahashi A, Zee O, Seyama T, Hong J, Ohuchi K, Hirasawa N.
|
| タイトル |
Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFRalpha.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRalpha) causes eosinophilic leukemia EoL-1 cells to proliferate. Recently, we demonstrated that histone deacetylase inhibitors suppressed this proliferation and induced the differentiation of EoL-1 cells into eosinophils in parallel with a decrease in the level of FIP1L1-PDGFRalpha. In this study, we analyzed the mechanism by which FIP1L1-PDGFRalpha induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFRalpha inhibitor imatinib inhibited the proliferation of EoL-1 cells and decreased the level of the oncoprotein c-Myc as well as the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK). The proliferation of EoL-1 cells and expression of c-Myc were also inhibited by the MEK inhibitor U0126 and JNK inhibitor SP600125. The expression of the eosinophilic differentiation marker CCR3 was not induced by imatinib. These findings suggest that FIP1L1-PDGFRalpha induces the proliferation of EoL-1 cells through the induction of c-Myc expression via ERK and JNK signaling pathways, but is not involved in the inhibition of differentiation toward mature eosinophils.
|
| 巻・号 |
366(4)
|
| ページ |
1007-11
|
| 公開日 |
2008-2-22
|
| DOI |
10.1016/j.bbrc.2007.12.063
|
| PII |
S0006-291X(07)02691-5
|
| PMID |
18086564
|
| MeSH |
Benzamides
Butadienes / pharmacology
Cell Differentiation / drug effects
Cell Line
Cell Proliferation / drug effects
Hypereosinophilic Syndrome / enzymology
Hypereosinophilic Syndrome / pathology*
Imatinib Mesylate
Mitogen-Activated Protein Kinases / metabolism
Nitriles / pharmacology
Oncogene Proteins, Fusion / metabolism*
Phosphorylation / drug effects
Piperazines / pharmacology
Proto-Oncogene Proteins c-myc / metabolism
Pyrimidines / pharmacology
Receptor, Platelet-Derived Growth Factor alpha / metabolism*
Receptors, CCR3 / metabolism
mRNA Cleavage and Polyadenylation Factors / metabolism*
|
| IF |
2.985
|
| 引用数 |
8
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
