IL-6-induced activation of MYC is responsible for the down-regulation of CD33 expression in CD33+ myeloma cells.
Int J Hematol
; 89(3): 310-318, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19259613
ABSTRACT
Human myeloma cells from about 10% of cases with multiple myeloma expressed CD33 and had monocytoid morphology with convoluted nuclei, and all these patients had no increase in serum CRP values. In CD33(+) myeloma cells as well as myeloma cell lines, CD33 expression levels were correlated with the increased expression levels of CEBPA (C/EBPalpha). This correlation was confirmed by the finding that transfection with the CEBPA gene induced CD33 expression in a CD33(-) myeloma cell line. As suggested by the lack of an increase in serum CRP values in CD33(+) myelomas, IL-6 down-regulated the expression of CD33 in CD33(+) myeloma cell lines along with the down-regulation of CEBPA gene expression. Cucurbitacin I (STAT3 inhibitor), but not U0126 (MAPK inhibitor), could abolish the effect of IL-6. Furthermore, IL-6 up-regulated the expression of MYC via STAT3 phosphorylation and MYC bound to the promoter region of the CEBPA gene followed by the down-regulation of CEBPA expression. It was confirmed that introduction of shRNA for MYC into a CD33(+) myeloma cell line blocked the IL-6-induced down-regulation of CD33 and CEBPA expression. Therefore, these results indicate that IL-6 can reverse the expression level of CD33 by up-regulating MYC followed by the down-regulation of CEBPA expression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Diferenciação Mielomonocítica
/
Antígenos CD
/
Interleucina-6
Limite:
Humans
Idioma:
En
Revista:
Int J Hematol
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão