Abl kinase but not PI3-kinase links to the cytoskeletal defects in Bcr-Abl transformed cells.

I. Gaston, P. E. Stenberg, A. Bhat, Brian Druker

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: The purpose of this study was to investigate the contribution of Abl kinase and phosphatidylinositol 3-kinase (PI3-kinase) to the altered adhesive properties and cytoskeletal defects in a Bcr-Abl transformed fibroblast cell model. MATERIALS AND METHODS: Two fibroblast cell lines stably transfected with Bcr-Abl were compared to their parental counterparts for alterations in their adhesive properties in an attachment assay and for abnormalities in their cytoskeletal architecture by immunofluorescence microscopy. Cells then were treated with specific inhibitors of either the Abl kinase CGP57148 or the PI3-kinase LY294002 to determine whether these treatments would restore normal cytoarchitecture and adhesion. RESULTS: Significant defects in cytoskeletal architecture were observed using this fibroblast model of Bcr-Abl expression. Specific changes include loss of stress fibers and focal adhesions, which correlated with an adhesive defect. Treatment of Bcr-Abl expressing cells with CGP57148, but not LY294002, resulted in reversion of cells to a near-normal phenotype, as assessed by immunofluorescence and attachment of Bcr-Abl transformed fibroblasts. CONCLUSIONS: Our studies demonstrate that Bcr-Abl tyrosine kinase but not PI3- kinase activity is required for maintenance of cytoskeletal rearrangements resulting from Bcr-Abl expression. Further, inhibition of Abl kinase restored normal adhesive properties to the Bcr-Abl-expressing cells, demonstrating the contribution of Bcr-Abl kinase activity to abnormal cytoskeletal function.

Original languageEnglish (US)
Pages (from-to)351
Number of pages1
JournalExperimental Hematology
Volume28
Issue number3
StatePublished - Mar 2000

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Phosphatidylinositol 3-Kinase
Phosphotransferases
Adhesives
Fibroblasts
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
bcr-abl Fusion Proteins
Stress Fibers
Focal Adhesions
Phosphatidylinositol 3-Kinases
Fluorescence Microscopy
Fluorescent Antibody Technique
Maintenance
Phenotype
Cell Line
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Abl kinase but not PI3-kinase links to the cytoskeletal defects in Bcr-Abl transformed cells. / Gaston, I.; Stenberg, P. E.; Bhat, A.; Druker, Brian.

In: Experimental Hematology, Vol. 28, No. 3, 03.2000, p. 351.

Research output: Contribution to journalArticle

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