Activation of protein kinase C enhances TNF-alpha-induced differentiation by preventing apoptosis via rapid up-regulation of c-Myc protein expression in HL-60 cells.
Leuk Lymphoma
; 44(3): 497-503, 2003 Mar.
Article
em En
| MEDLINE
| ID: mdl-12688321
ABSTRACT
Tumor necrosis factor-alpha (TNF-alpha) induces both rapid onset of apoptosis and monocytic differentiation in HL-60 human myeloid leukemia cells. In this study, we examined the effect of activation of protein kinase C (PKC) in c-Myc protein expression in association with the induction of apoptosis and differentiation in TNF-alpha-treated HL-60 cells. Pretreatment with phorbol 12-myristate 13-acetate (PMA), an activator of PKC, prevented TNF-alpha-induced rapid onset of apoptosis, which occurs at 3 h culture with TNF-alpha, concomitantly with the up-regulation of c-Myc protein expression. In addition, PMA enhanced TNF-a-induced differentiation at 24h treatment. This was documented by the expression of integrin Mac-1 molecule (CD11b) on the cell surface and the cellular adhesion to the plastic bottom of the flask, indicating the differentiation along with the monocyte/macrophage lineage. These results indicate that activation of PKC not only counteracts apoptosis but also enhances differentiation in TNF-alpha-treated HL-60 cells. Up-regulation of c-Myc protein evoked by pretreatment with PMA for a short time could disturb the signaling pathway of the ceramide and sphingosine, which are known to function as the endogenous modulators mediating the apoptotic signal of TNF-alpha. Our results strongly suggest the role of c-Myc protein as a mediator of cytoprotective effect of PKC pathway, and PKC pathway opposes apoptosis and consequently undergo differentiation via rapid up-regulated c-Myc protein expression during TNF-alpha signaling of HL-60 cells. Our findings provide a new insight for a role of PKC and c-Myc protein with special reference to the regulatory mechanisms in the decision of cellular fate, differentiation or apoptosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
/
Acetato de Tetradecanoilforbol
/
Regulação Neoplásica da Expressão Gênica
/
Genes myc
/
Proteínas Proto-Oncogênicas c-myc
/
Fator de Necrose Tumoral alfa
/
Apoptose
/
Células HL-60
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Leuk Lymphoma
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Japão