LukS-PV induces differentiation by activating the ERK signaling pathway and c-JUN/c-FOS in human acute myeloid leukemia cells.
Int J Biochem Cell Biol
; 76: 107-14, 2016 07.
Article
em En
| MEDLINE
| ID: mdl-27102414
ABSTRACT
LukS-PV, a component of Panton-Valentine leukocidin, is a pore-forming cytotoxin secreted by Staphylococcus aureus. Here we examined the potential effect of LukS-PV in differentiation of human leukemia cells and the underlying mechanism. We found that LukS-PV could induce differentiation of human acute myeloid leukemia (AML) cells, including AML cell lines and primary AML blasts, as determined by morphological changes, phagocytosis assay and expression of CD14 and CD11b surface antigens. In addition, LukS-PV activated the extracellular signal-regulated kinase (ERK) pathway and significantly upregulated the phosphorylation of c-JUN and c-FOS transcriptional factors in the process of differentiation. Inhibiting ERK pathway activation with U0126 (a MEK1/2 inhibitor) markedly blocked LukS-PV-induced differentiation and decreased the phosphorylation of c-JUN and c-FOS. These findings demonstrate an essential role for the ERK pathway together with c-JUN and c-FOS in the differentiation activity of LukS-PV. Taken together, our data suggest that LukS-PV could be a potential candidate as a differentiation-inducing agent for the therapeutic treatment of AML.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Staphylococcus aureus
/
Proteínas de Bactérias
/
Leucemia Mieloide Aguda
/
Diferenciação Celular
/
Proteínas Proto-Oncogênicas c-jun
/
Proteínas Proto-Oncogênicas c-fos
/
Sistema de Sinalização das MAP Quinases
/
Leucocidinas
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article