Effects of the Tyrosine Kinase Inhibitor Imatinib Mesylate on a Bcr-Abl-Positive Cell Line: Suppression of Autonomous Cell Growth but No Effect on Decreased Adhesive Property and Morphological Changes

  • Toshio Nishihara
  • Yasuo Miura
  • Yumi Tohyama
  • Chisato Mizutani
  • Terutoshi Hishita
  • Satoshi Ichiyama
  • Takashi Uchiyama
  • Kaoru Tohyama
Progress in Hematology

Abstract

Expression of the Bcr-Abl oncoprotein alters various aspects of hematopoietic cells. We investigated the effects of a Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate, on the proliferation, adhesive properties, and morphology of a Bcr-Abl-transferred cell line, TF-1 Bcr-Abl, in comparison with parental TF-1. First, the factor-independent growth of TF-1 Bcr-Abl was inhibited in the presence of imatinib mesylate, but this inhibition was overcome by addition of exogenous granulocyte-macrophage colony-stimulating factor. Imatinib mesylate remarkably reduced tyrosine phosphorylation of Bcr-Abl, Cbl, and Crkl in a time-dependent manner, and their complex formation also was affected. Imatinib mesylate inhibited activation of Stat5 rather than the MEK-ERK1/2 pathway. TF-1 Bcr-Abl cells exhibited a round shape, unlike TF-1, and the adhesive property to fibronectin was much lower than that of TF-1. Although the Bcr-Abl oncoprotein may be involved negatively in cell adhesion, the decreased adhesion and altered morphology of TF-1 Bcr-Abl cells were minimally affected by imatinib mesylate and seemed independent of Bcr-Abl kinase activity. The present data indicated that the Bcr-Abl-specific kinase inhibitor cannot control Bcr-Abl-induced cell alterations other than autonomous growth.Int J Hematol. 2003;78:233-240.

Key words

Bcr-Abl Autonomous growth Tyrosine kinase inhibitor Cell adhesion 

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Copyright information

© 2003 The Japanese Society of Hematology 2003

Authors and Affiliations

  • Toshio Nishihara
    • 1
  • Yasuo Miura
    • 1
  • Yumi Tohyama
    • 1
  • Chisato Mizutani
    • 1
  • Terutoshi Hishita
    • 1
  • Satoshi Ichiyama
    • 2
  • Takashi Uchiyama
    • 1
  • Kaoru Tohyama
    • 2
  1. 1.Department of Hematology and OncologyKyoto UniversityKyotoJapan
  2. 2.Department of Laboratory Medicine, Graduate School of MedicineKyoto UniversityKyotoJapan

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