Bcr/Abl expression stimulates integrin function in hematopoietic cell lines.
AUTOR(ES)
Bazzoni, G
RESUMO
Cell adhesion to the extracellular matrix is largely mediated by adhesion molecules of the integrin family and is often diminished upon oncogenic transformation. However, we show here that the chronic myelogenous leukemia oncogene Bcr/Abl has positive effects on VLA-4 and VLA-5 integrin function. The presence of Bcr/Abl in the GM-CSF- or IL-3-dependent hematopoietic cell lines MO7e, 32D, and BaF/3 enhanced cell binding to both soluble and immobilized fibronectin. The effect was due to enhanced function of the VLA-5 integrin fibronectin receptor and not to increased surface expression. In parallel, Bcr/Abl stimulated cell adhesion to the VLA-4 integrin ligand VCAM-1. Stimulation of VLA-5 function directly correlated with induction of Bcr/Abl tyrosine kinase activity in a temperature-sensitive kinase mutant. Thus, Bcr/Abl stimulates integrin-dependent cell adhesion, by a mechanism involving increased ligand binding, with the tyrosine kinase activity of Bcr/Abl likely playing a key role. Consistent with these results, hematopoietic precursor cells from chronic myelogenous leukemia patients also showed increased adhesion to fibronectin.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=507458Documentos Relacionados
- Clonal lymphoid progenitor cell lines expressing the BCR/ABL oncogene retain full differentiative function.
- BCR/ABL induces multiple abnormalities of cytoskeletal function.
- BCR/ABL inhibition by an escort/phosphatase fusion protein
- Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias
- Molecular approach to diagnose BCR/ABL negative chronic myeloproliferative neoplasms