IGF-I receptor activation and BCL-2 overexpression prevent early apoptotic events in human neuroblastoma.
The type I insulin-like growth factor receptor (IGF-IR) is important for mitogenesis, transformation, and survival of tumor cells. The current study examines the effect of IGF-IR expression and activation on apoptosis in SHEP human neuroblastoma cells. SHEP cells undergo apoptosis which is prevented by IGF-I addition or overexpression of the IGF-IR (SHEP/IGF-IR cells). High mannitol treatment activates caspase-3 by 1 h in SHEP cells while caspase-3 activation is delayed by 3 h in SHEP/IGF-IR cells. Transfection with Bcl-2 (SHEP/Bcl-2 cells) prevents serum withdrawal and mannitol induced apoptosis and caspase-3 activation. Mannitol induces mitochondrial membrane depolarization in both SHEP and SHEP/IGF-IR cells. IGF-IR activation or overexpression of Bcl-2 in SHEP cells prevents mitochondrial membrane depolarization. Collectively, these results suggest that IGF-IR or Bcl-2 overexpression in neuroblastoma cells promotes cell survival by preventing mitochondrial membrane depolarization and caspase-3 activation, ultimately leading to increased tumor growth.
van Golen
C M
CM
Department of Neurology and Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109-0588, USA.
Castle
V P
VP
Feldman
E L
EL
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D048429:Cell Size; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D004792:Enzyme Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D008353:Mannitol; D017526:Receptor, IGF Type 1; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases