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Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells

TitleSilencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2005
AuthorsTanno, Barbara, Cesi Vincenzo, Vitali Roberta, Sesti F., Giuffrida M.L., Mancini C., Calabretta B., and Raschellà G.
JournalCell Death and Differentiation
Volume12
Pagination213-223
ISSN13509047
KeywordsApoptosis, article, binding affinity, cell culture, cell differentiation, cell function, cell growth, cell proliferation, Cell Survival, controlled study, Cultured, gene silencing, genetic transfection, growth inhibition, human, human cell, Humans, Immunoprecipitation, Insulin-Like Growth Factor Binding Protein 5, Messenger, messenger RNA, microRNA, MicroRNAs, nerve cell differentiation, Neuroblastoma, neuroblastoma cell, priority journal, protein expression, protein function, recombinant protein, Recombinant Proteins, reverse transcription polymerase chain reaction, RNA, RNA extraction, RNA Interference, signal transduction, Small Interfering, Small interfering RNA, somatomedin binding protein 5, Somatomedins, Transfection, Tumor Cells, Western blotting, X irradiation, X-Rays
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. © 2005 Nature Publishing Group All rights reserved.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-14944369834&doi=10.1038%2fsj.cdd.4401546&partnerID=40&md5=3fb7016e7d498721a0718055e6578100
DOI10.1038/sj.cdd.4401546
Citation KeyTanno2005213