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Title: Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFR{alpha}

The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor {alpha} (PDGFR{alpha}) 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-PDGFR{alpha}. In this study, we analyzed the mechanism by which FIP1L1-PDGFR{alpha} induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFR{alpha} 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-PDGFR{alpha} 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.
Authors:
; ; ; ;  [1] ;  [2] ;  [3] ; ;  [1] ;  [4] ;  [5]
  1. Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578 (Japan)
  2. Laboratory of Pharmacognosy, Graduate School of Pharmacy, Sungkyunkwan University, Suwon (Korea, Republic of)
  3. Faculty of Pharmacy, Yasuda Women's University, Hiroshima (Japan)
  4. (Japan)
  5. Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578 (Japan), E-mail: hirasawa@mail.pharm.tohoku.ac.jp
Publication Date:
OSTI Identifier:
21043631
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 366; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2007.12.063; PII: S0006-291X(07)02691-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; EOSINOPHILS; GROWTH FACTORS; INHIBITION; LEUKEMIA; PHOSPHORYLATION; RECEPTORS; TYROSINE