IGF-I receptor activation and BCL-2 overexpression prevent early apoptotic events in human neuroblastoma

Cell Death Differ. 2000 Jul;7(7):654-65. doi: 10.1038/sj.cdd.4400693.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / physiology*
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Size
  • Culture Media, Serum-Free
  • Enzyme Activation
  • Enzyme Precursors / antagonists & inhibitors
  • Enzyme Precursors / metabolism
  • Humans
  • Mannitol / pharmacology
  • Mitochondria / metabolism
  • Neuroblastoma / enzymology
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Recombinant Proteins / metabolism
  • Transfection
  • Tumor Cells, Cultured / drug effects

Substances

  • Caspase Inhibitors
  • Culture Media, Serum-Free
  • Enzyme Precursors
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • Mannitol
  • Receptor, IGF Type 1
  • CASP3 protein, human
  • Caspase 3
  • Caspases