Expression level of Bcl-2 determines anti- or proapoptotic function

Cancer Res. 1999 Aug 15;59(16):4119-28.

Abstract

Bcl-2 is an oncogene with antiapoptotic function. However, Bcl-2 is converted to a Bax-like death effector by caspases, suggesting that the expression of Bcl-2 may not favor the growth of cancers. We introduced the Bcl-2 gene to gliomas via adenovirus (Adv; Adv-Bcl-2) with the Adv for Fas (Adv-Fas) and the Adv for Fas ligand (Adv-FL) to evaluate the antiapoptotic function of Bcl-2. In U251 glioblastoma cells, Bcl-2 at a low level of expression repressed apoptosis induced by Adv-Fas and Adv-FL, whereas Bcl-2 at a high level of expression did not. On the other hand, Bcl-X(L) showed antiapoptotic function against Fas-mediated apoptosis, irrespective of its expression level. In glioblastoma cells, induction of Bcl-2 alone at a high level induced apoptosis, whereas induction of Bcl-X(L) alone did not. As the multiplicity of infection of Adv-Bcl-2 was increased, the quantity of a cleaved product of Bcl-2 increased. Induction of caspase-inhibitory genes (CrmA and p35) inhibited apoptosis induced by Adv-Bcl-2. Induction of Bcl-2 led to alteration of the membrane potential and structure of the mitochondria. In summary, although Bcl-2 at a low level of expression was antiapoptotic, Bcl-2 at a high level of expression was proapoptotic to Fas-mediated apoptosis. Overexpression of Bcl-X(L) was consistently antiapoptotic to Fas-mediated apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Fas Ligand Protein
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • Membrane Glycoproteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Tumor Cells, Cultured
  • fas Receptor / genetics

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor