The insulin-like growth factor (IGF) axis is frequently activated in neuroblastoma (NB) tumors and cell lines. We show that silencing endogenous expression of IGF Binding Protein-5 (IGFBP-5) in NB cells by using microRNA and siRNA causes mitochondrial apoptosis that is characterized by: (a) release of cytochrome C in the cytoplasm and activation of caspase 9; (b) Erk1 and Erk2 inhibition; and (c) upregulation of pro-apoptotic proteins Bim and Bax. Bim upregulation is caused, at least in part, by protein stabilization that may depend on inhibition of Erk1 and Erk2. Of interest, Bim knock-down by siRNA decreases apoptosis in IGFBP-5-interfered cells. Thus, inhibition of endogenously produced IGFBP-5 is associated with Bim-dependent apoptosis in NB cells. (c) 2006 Elsevier Inc. All rights reserved.
Bim-dependent apoptosis follows IGFBP-5 down-regulation in neuroblastoma cells / Barbara, Tanno; Roberta, Vitali; D., De Arcangelis; Camillo, Mancini; Patrizia, Eleuteri; Dominici, Carlo; G., Raschella'. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 351:2(2006), pp. 547-552. [10.1016/j.bbrc.2006.10.062]
Bim-dependent apoptosis follows IGFBP-5 down-regulation in neuroblastoma cells
D. De Arcangelis;DOMINICI, Carlo;
2006
Abstract
The insulin-like growth factor (IGF) axis is frequently activated in neuroblastoma (NB) tumors and cell lines. We show that silencing endogenous expression of IGF Binding Protein-5 (IGFBP-5) in NB cells by using microRNA and siRNA causes mitochondrial apoptosis that is characterized by: (a) release of cytochrome C in the cytoplasm and activation of caspase 9; (b) Erk1 and Erk2 inhibition; and (c) upregulation of pro-apoptotic proteins Bim and Bax. Bim upregulation is caused, at least in part, by protein stabilization that may depend on inhibition of Erk1 and Erk2. Of interest, Bim knock-down by siRNA decreases apoptosis in IGFBP-5-interfered cells. Thus, inhibition of endogenously produced IGFBP-5 is associated with Bim-dependent apoptosis in NB cells. (c) 2006 Elsevier Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
