The suppression of drug-induced apoptosis by activation of v-ABL protein tyrosine kinase.
Cancer Res
; 54(19): 5131-7, 1994 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-7923130
ABSTRACT
Cells with a temperature-sensitive mutant of the v-abl oncoprotein (IC.DP) were treated with the anticancer drugs melphalan or hydroxyurea. At the restrictive temperature for v-ABL protein tyrosine kinase activity, drug-treated IC.DP cells died by apoptosis. In contrast, apoptotic cell death induced by either drug was suppressed when v-ABL was active. However, melphalan-induced accumulation of cells in the S and G2-M phases of the cell cycle was unaffected by v-ABL activation. Moreover, the continuous presence of v-ABL activity was necessary to suppress apoptosis. This suggested that melphalan had interacted with DNA and that v-ABL activity prevented the coupling of drug-induced damage to the apoptotic pathway. IC.DP cells exhibited similar levels and subcellular localization of the BCL-2 protein irrespective of v-ABL activation status, thus v-ABL-mediated cell survival appeared to be independent of BCL-2.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Proteínas Oncogênicas v-abl
/
Apoptose
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1994
Tipo de documento:
Article
País de afiliação:
Reino Unido