Characterization of factor-independent variants derived from TF-1 hematopoietic progenitor cells: the role of the Raf/MAP kinase pathway in the anti-apoptotic effect of GM-CSF.
Oncogene
; 14(6): 721-8, 1997 Feb 13.
Article
em En
| MEDLINE
| ID: mdl-9038380
ABSTRACT
Human hematopoietic progenitor cells (TF-1) undergo apoptosis upon deprivation of their dependent cytokine. In this report, we have isolated and characterized some spontaneously derived cytokine-independent variants from TF-1 cells. Analysis of several signaling molecules known to be activated by the GM-CSF pathway revealed that two non-autocrine variants were still responsive to GM-CSF stimulation. However, both variants, without ligand stimulation, already had some activated forms of Raf and MAP kinases. Given current knowledge, the activated Raf/MAP kinase pathway was likely to be responsible for the survival of both variants in the cytokine-free medium. However, the growth of hybrids between wild type and either variant was unexpectedly dependent on GM-CSF. Both variants like the wild type cells were still susceptible to apoptosis induced by other stimuli. These results suggest that either the activated Raf/MAP kinase pathway in both variants is not sufficient to repress the 'two-fold' death signals generated from the hybrids or that there is another mechanism that is responsible for the factor-independent growth of both variants.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Transdução de Sinais
/
Fator Estimulador de Colônias de Granulócitos e Macrófagos
/
Proteínas Proto-Oncogênicas
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Proteínas Serina-Treonina Quinases
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Apoptose
/
Proteínas Quinases Dependentes de Cálcio-Calmodulina
Limite:
Humans
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article