Abl kinase but not PI3-kinase links to the cytoskeletal defects in Bcr-Abltransformed cells (vol 28, pg 77, 2000)

Objective. The purpose of this study was to investigate the contribution of Abl kinase and phosphatidylinositol 3-kinase (PI3-kinase) to the altered a dhesive properties and cytoskeletal defects in a Bcr-Abl transformed fibrob last cell model. Materials and Methods. Two fibroblast cell lines stably transfected with Bc r-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 nor mal cytoarchitecture and adhesion. Results. Significant defects in cytoskeletal architecture were observed usi ng this fibroblast model of Bcr-Abl expression. Specific changes include lo ss of stress fibers and focal adhesions, which correlated with an adhesive defect, Treatment of Bcr-Abl expressing cells with CGP57148, but not LY2940 02, 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 P I3- kinase activity is required for maintenance of cytoskeletal rearrangeme nts resulting from Bcr-Abl expression. Further, inhibition of Abl kinase re stored normal adhesive properties to the Bcr-Abl-expressing cells, demonstr ating the contribution of Bcr-Abl kinase activity to abnormal cytoskeletal function, (C) 2000 International Society for Experimental Hematology. Publi shed by Elsevier Science Inc.