Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells.
Cell Death Differ
; 12(3): 213-23, 2005 Mar.
Article
en En
| MEDLINE
| ID: mdl-15618969
ABSTRACT
Signal transduction through the IGF axis is implicated in proliferation, differentiation and survival during development and adult life. The IGF axis includes the IGF binding proteins (IGFBPs) that bind IGFs with high affinity and modulate their activity. In neuroblastoma (NB), a malignant childhood tumor, we found that IGFBP-5 is frequently expressed. Since NB is an IGF2-sensitive tumor, we investigated the relevance and the function of endogenous IGFBP-5 in LAN-5 and in SY5Y(N) cell lines transfected with micro and small interfering RNAs directed to IGFBP-5 mRNA. Cells in which IGFBP-5 expression was suppressed were growth-inhibited and more prone to apoptosis than the parental cell line and controls. Apoptosis was further enhanced by X-ray irradiation. The ability of these cells to undergo neuronal differentiation was impaired after IGFBP-5 inhibition but the effect was reversed by exposure to recombinant IGFBP-5. Together, these data demonstrate the importance of IGFBP-5 for NB cell functions and suggest that IGFBP-5 might serve as a novel therapeutic target in NB.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina
/
MicroARNs
/
Interferencia de ARN
/
Neuroblastoma
Límite:
Humans
Idioma:
En
Revista:
Cell Death Differ
Año:
2005
Tipo del documento:
Article
País de afiliación:
Italia