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
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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.
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- 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
International Journal of Hematology
Volume 78, Issue 3 , pp 233-240
- Cover Date
- Print ISSN
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- Autonomous growth
- Tyrosine kinase inhibitor
- Cell adhesion
- Industry Sectors
- Author Affiliations
- 1. Department of Hematology and Oncology, Kyoto University, Kyoto, Japan
- 2. Department of Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan