期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 336, 期 3, 页码 942-951出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2005.08.201
关键词
chronic myelogenous leukemia; imatinib mesylate; proteomics; two-dimensional gel electrophoresis; tyrosine phosphorylation
Bcr-Ab1 fusion tyrosine kinase contributes to leukemic transformation. Imatinib mesylate inhibits Bcr-Ab1 tyrosine kinase, resulting in a blockage of tyrosine phosphorylation in its downstream pathways. We analyzed the alteration of tyrosine phosphorylation, on BCR1 ABL(+) chronic myelogenous leukemia cells, after treatment with imatinib mesylate. Data were collected using a two-dimensional gel electrophoresis followed by Western blot and mass spectrometry. The inhibition of Bcr-Ab1 tyrosine kinase by 2.5 mu M imatinib mesylate caused both cell cycle arrest in the G(0)/G(1) phase and increased the portion of apoptotic cells. As a result, the population of leukemic cells decreased by 30% and 70% compared to controls at 24 and 72 h, respectively. Furthermore, treatment with imatinib mesylate altered tyrosine phosphorylation of 24 protein spots as the incubation time proceeded from 0 to 24 and 72 h. Ten of the 24 protein spots are visible at all three times. Four are detectable at both the 0 and 24 h points in time. Eight were detectable only at time 0. (c) 2005 Elsevier Inc. All rights reserved.
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