Antiproliferative effect of a vitamin D3 analog, EB1089, on HL-60 cells by the induction of TGF-beta receptor.
Leuk Res
; 23(12): 1105-12, 1999 Dec.
Article
em En
| MEDLINE
| ID: mdl-10613355
ABSTRACT
EB1089 is a novel 1,25(OH)2D3 analog that has more potent antitumor properties with reduced hypercalcemic effects than 1,25(OH)2D3. We investigated the role of transforming growth factor-beta1 (TGF-beta1) in the growth inhibition of human acute myeloid leukemia cell line, HL-60, by EB1089. Clonal growth of HL-60 cells was inhibited in a dose-dependent manner by EB1089. Although TGF-beta1 alone slightly inhibited proliferation of HL-60 cells, the addition of TGF-beta1 into culture treated with 10(-8) M of EB1089 showed a significant synergistic antiproliferative effect in a dose-dependent manner. EB1089 up-regulated the expression of TGF-beta receptor type I (TGF-beta RI), type II (TGF-beta RII) and TGF-beta1. Antiproliferative effect of EB1089 was partially reversed by TGF-beta1 neutralizing antibody (anti-TGF-beta1). Vitamin D receptor (VDR) expression was increased by TGF-beta1, suggesting synergistic action of TGF-beta1 and EB1089. Combined treatment of EB1089 and TGF-beta1 resulted in an increased expression of cyclin-dependent kinase inhibitor (CDKI), p27 protein, compared to either ligand alone. Up-regulation of p27 protein expression by either TGF-beta1 or EB1089 was reduced by anti-TGF-beta1. These findings suggest that TGF-beta1 is involved in the antiproliferative effect of EB1089 on HL-60 cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calcitriol
/
Fator de Crescimento Transformador beta
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Proteínas Serina-Treonina Quinases
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Receptores de Fatores de Crescimento Transformadores beta
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Proteínas de Ciclo Celular
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Células HL-60
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Receptores de Ativinas Tipo I
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Proteínas Supressoras de Tumor
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Inibidores do Crescimento
Limite:
Humans
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
1999
Tipo de documento:
Article