Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+

Oncogene. 1996 Jun 6;12(11):2259-66.


Bcl-2 expression is associated with the progression of prostate cancer from androgen-dependence to androgen-independence. Bcl-2 is an integral membrane protein which localizes to mitochondria, endoplasmic reticulum, and the nuclear envelope. Using spectrofluorometry and laser confocal microscopy, the ability of bcl-2 to modulate intracellular Ca2+ was examined in the Dunning G prostate carcinoma cell line following apoptosis induction by adriamycin. Adriamycin and thapsigargin, an endoplasmic reticulum Ca2+-pump inhibitor, were effective inducers of apoptosis in control, but not bcl-2 transfected, cells. Treatment with adriamycin was accompanied by a sustained rise in cytoplasmic Ca2+ in control and bcl-2 transfected cells. An increase in intranuclear Ca2+ was observed in control cells only. Apoptosis induction by thapsigargin was associated with an increase in cytoplasmic Ca2+ in control cells that was not detected in the resistant bcl-2 transfectants. Ca2+ was excluded from nuclei isolated from bcl-2 expressing cells, but was sequestered in control nuclei, following the addition of ATP. These findings suggest that bcl-2 may regulate levels of intranuclear Ca2+ independently of cytosolic Ca2+ levels. The ability of bcl-2 to modulate, directly or indirectly, sustained increases in both cytosolic and intranuclear Ca2+ may provide a common basis for bcl-2 function in different subcellular compartments.

Publication types

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

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Calcium / metabolism*
  • Cell Nucleus / metabolism*
  • Cytosol / metabolism*
  • DNA, Neoplasm / metabolism
  • Doxorubicin / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Male
  • Microscopy, Confocal
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2
  • Rats
  • Terpenes / pharmacology
  • Thapsigargin
  • Tumor Cells, Cultured


  • Antibiotics, Antineoplastic
  • DNA, Neoplasm
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Terpenes
  • Thapsigargin
  • Doxorubicin
  • Calcium