Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFRα

Kenji Ishihara, Hajime Kitamura, Kenji Hiraizumi, Motoko Kaneko, Aki Takahashi, Ok Pyo Zee, Toshio Seyama, Jang Ja Hong, Kazuo Ohuchi, Noriyasu Hirasawa

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor α (PDGFRα) 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-PDGFRα. In this study, we analyzed the mechanism by which FIP1L1-PDGFRα induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFRα 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-PDGFRα 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.

Original languageEnglish
Pages (from-to)1007-1011
Number of pages5
JournalBiochemical and biophysical research communications
Volume366
Issue number4
DOIs
Publication statusPublished - 2008 Feb 22

Keywords

  • EOL-1 cells
  • FIP1L1-PDGFRα
  • Histone deacetylase inhibitor
  • Imatinib
  • Proliferation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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