bcl-2 over-expression delays radiation-induced apoptosis without affecting the clonogenic survival of human prostate cancer cells

Int J Cancer. 1997 Jan 27;70(3):341-8. doi: 10.1002/(sici)1097-0215(19970127)70:3<341::aid-ijc16>3.0.co;2-i.


In this study we evaluated the effect of over-expression of the bcl-2 gene, a potent apoptosis suppressor, on radiation-induced apoptotic cell death in 2 human prostate cancer cell lines, androgen-independent PC-3 cells and androgen-sensitive LNCaP cells. Cells were transfected with the bcl-2 gene and bcl-2 transfectant clones isolated under neomycin selection; bcl-2 gene integration and level of mRNA and protein expression in the cloned transfectants were examined by Southern, Northern and Western blot analyses, respectively. Parental, neo control and bcl-2-expressing cells were exposed to single or fractionated doses of ionizing irradiation, and the cellular response to radiation was determined at 24, 48 and 72 hr post-irradiation, on the basis of: (i) loss of cell viability, (ii) clonogenic survival and (iii) induction of apoptotic DNA fragmentation. At 24 hr post-irradiation all cell lines, i.e., parental and bcl-2 transfectants, failed to form colonies, though the majority of bcl-2-expressing cells did not exhibit apoptotic morphology; bcl-2 over-expression in both cell lines reduced apoptosis 48 hr post-irradiation from 20-25% to 5% at a dose of 2,000 cGy. By 72 hr, bcl-2 over-expression afforded a 3-fold protection from radiation-induced apoptosis. There was no significant difference, however, in the clonogenic survival of the parental and bcl-2-expressing cells. Furthermore, there was a 24 hr delay in induction of the apoptosis marker gene SGP-2/TRPM-2 in the bcl-2-expressing cells, co-incidental with the delay in apoptotic DNA fragmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / radiation effects*
  • Cell Division / radiation effects
  • Cell Survival / radiation effects
  • Clusterin
  • DNA Fragmentation
  • Genes, bcl-2*
  • Glycoproteins / metabolism
  • Humans
  • Male
  • Molecular Chaperones*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Radiation Dosage
  • Transfection
  • Tumor Stem Cell Assay


  • CLU protein, human
  • Clusterin
  • Glycoproteins
  • Molecular Chaperones
  • Proto-Oncogene Proteins c-bcl-2