ts BCR-ABL kinase activation confers increased resistance to genotoxic damage via cell cycle block
| Autor: | K, Nishii, J H, Kabarowski, D L, Gibbons, S D, Griffiths, I, Titley, L M, Wiedemann, M F, Greaves |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
G2 Phase
Phosphodiesterase Inhibitors Fusion Proteins bcr-abl G1 Phase Temperature bcl-X Protein Mitosis Apoptosis Antineoplastic Agents Phytogenic Radiation Tolerance Cell Line Proto-Oncogene Proteins c-bcl-2 Caffeine Enzyme Induction Proto-Oncogene Proteins Interleukin-3 Phosphorylation Protein Kinases Etoposide bcl-2-Associated X Protein |
| Zdroj: | Oncogene. 13(10) |
| ISSN: | 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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