Bim-dependent apoptosis follows IGFBP-5 down-regulation in neuroblastoma cells.
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.
Tanno
Barbara
B
ENEA, Research Center Casaccia, Section of Toxicology and Biomedical Sciences, Rome, Italy.
Vitali
Roberta
R
De Arcangelis
Davide
D
Mancini
Camillo
C
Eleuteri
Patrizia
P
Dominici
Carlo
C
Raschellà
Giuseppe
G
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology; D009447:Neuroblastoma; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D018975:Insulin-Like Growth Factor Binding Protein 5; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051028:bcl-2-Associated X Protein; D048049:Extracellular Signal-Regulated MAP Kinases