Difference in response to colony-stimulating factors and involvement of protein kinase C signal transduction system in three subclones from the ME-1 cell line and two sublines

Kohsuke Yanagisawa, Masateru Sato, Takahiko Horiuchi, Hitoshi Hasegawa, Shigeru Fujita

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We previously established a cell line from a patient with acute myelomonocytic leukemia with eosinophilia (M4E0), ME-1. ME-1 cells are responsive to colony-stimulating factors (CSFs) such as interleukin-3 (IL- 3), IL-4, and granulocyte-macrophage CSF (GM-CSF), and exhibit monocyte- macrophage differentiation. We isolated three subclones, ME-F1 from ME-1, and ME-F2 and ME-F3 from two sublines of ME-1. These subclones had different morphologic, cytochemical, phenotypic, and cytogenetic features. They represented different monocytic-lineage differentiation stages and exhibited different responses to IL-3, GM-CSF, and especially IL-4, IL-3, GM- CSF, and IL-4 enhanced proliferation and differentiation to macrophage-like cells in the ME-F1 subclone. However, they enhanced only proliferation of ME-F2 cells and only differentiation to macrophage-like cells in the ME-F3 subclone. To elucidate possible differences in signal transduction mechanisms in ME-F1, ME-F2, and ME-F2 cells following stimulation by CSFs, we studied the effects of IL-3 and IL-4 on protein kinase C (PKC) activity. Both IL-3 and IL-4 induced a rapid, transient decrease of cytosolic PKC in ME-F1 cells, but did not affect PKC activity in ME-F2 and ME-F3 cells. The PKC inhibitors, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) and calphostin C inhibited IL-3-induced enhancement of proliferation and differentiation of ME-F1 cells, but did not inhibit enhancement of proliferation of ME-F2 cells and differentiation of ME-F3 cells. Our data suggest that PKC-dependent signal transduction is considerably related to IL- 3-induced proliferation and differentiation of ME-F1 cells. In addition, it was demonstrated that the two subclones, ME-F2 and ME-F3, lost one of the two responses of ME-F1 cells of CSFs, either proliferation or differentiation, and simultaneously lost PKC-dependent response to CSFs.

Original languageEnglish
Pages (from-to)84-93
Number of pages10
Issue number1
Publication statusPublished - Jul 1 1994
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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