Activated Ki-ras enhances sensitivity of ceramide-induced apoptosis without c-Jun NH2-terminal kinase/stress-activated protein kinase or extracellular signal-regulated kinase activation in human colon cancer cells.
Cancer Res
; 57(21): 4714-7, 1997 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-9354428
ABSTRACT
The activation of c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK) and/or extracellular signal-regulated kinase (ERK) is involved in ceramide-induced apoptosis in certain cells. To examine the relationship between activated Ki-ras-mediated signals and ceramide-induced apoptosis in human colon cancer cells, JNK/SAPK and ERK activity, as initiated by ceramide, was examined in HCT116, which has a mutation of Ki-ras at codon 13, and HCT116-derived clones, HKe-3 and HKh-2, in which activated Ki-ras was disrupted through gene targeting. In HKe-3 and HKh-2, the activity of JNK/SAPK increased significantly within 60 min following C2 ceramide stimulation, and some apoptosis followed. In contrast, C2 ceramide caused a marked apoptosis in HCT116, but activation of JNK/SAPK was not observed. C2 ceramide did not activate ERK in any of the cell lines. These results suggest that activated Ki-ras contributes to the sensitivity of ceramide-induced apoptosis without JNK/SAPK or ERK activation and that other signaling pathways involved in ceramide-induced apoptosis may be present in human colon cancer cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ceramidas
/
Genes ras
/
Apoptose
/
Neoplasias do Colo
/
Proteínas Quinases Dependentes de Cálcio-Calmodulina
/
Proteínas Proto-Oncogênicas c-raf
/
Proteínas Quinases Ativadas por Mitógeno
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Japão