ts BCR-ABL kinase activation confers increased resistance to genotoxic damage via cell cycle block.
Oncogene
; 13(10): 2225-34, 1996 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-8950990
ABSTRACT
Using a temperature-sensitive mutant of the p210 BCR-ABL gene, transfected into a growth factor-dependent cell line (BaF3), we show that transient BCR-ABL kinase expression increases single cell and clonogenic resistance to apoptosis arising from genotoxic damage induced by ionizing radiation and VP-16/etoposide. This effect is achieved in the absence of any detectable changes in the levels of BCL-2, BAX or BCL-x proteins and is independent of proliferative, MAP kinase-dependent effects of BCR-ABL kinase. In contrast to parental cells that transiently arrest in G2 and then apoptose, p210 BaF3 cells show a pronounced and sustained G2 arrest following radiation coupled with enhanced phosphorylation of cdc2. A cell cycle block in early M phase induced by the mitotic spindle poison, nocodazole, does not provide protection from apoptosis. Reversal of G2 arrest by caffeine abolishes the protective effect of BCR-ABL kinase. These data provide further insight into the transforming properties of BCR-ABL and are relevant to the clinical intransigence of Ph-positive leukaemias.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Fusão bcr-abl
/
Interleucina-3
/
Apoptose
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article