Loss of Bcl-2 in invasive breast cancer is associated with high rates of cell death, but also with increased proliferative activity

Br J Cancer. 1998 Mar;77(5):789-96. doi: 10.1038/bjc.1998.128.


Bcl-2 has been demonstrated to inhibit apoptosis in breast cancer cells in vitro, and the ratio between Bcl-2 and its proapoptotic homologue Bax seems to be an important determinant of cellular sensitivity to induction of apoptosis. However, little information is available on the relationship between Bcl-2 and the rate of apoptotic and necrotic cell death in breast tumours. From a series of 441 premenopausal, lymphnode-negative breast cancer patients, a subset of 49 tumours was selected in which immunostaining for the 26-kDa isoform of Bcl-2 was either absent (n = 23) or very high (n = 26). High expression of Bcl-2 was found to be strongly associated with low rates of apoptotic (P < 0.001) and necrotic cell death (P < 0.001). The mean value of the apoptotic index was 2.69%+/-1.40% in Bcl-2-negative tumours and 0.68%+/-1.00% in Bcl-2-positive tumours. Expression of the proapoptotic protein Bax correlated neither with Bcl-2 nor with the frequency of apoptotic cells. Immunostaining for the antiapoptotic Bcl-2 homologue BcI-X(L) correlated with Bcl-2 expression (P < 0.001) but not with apoptosis. High proliferation rate and high tumour grade (Bloom-Richardson) were strongly associated with absence of Bcl-2 expression (P< 0.001). p53 accumulation was associated with absence of Bcl-2 expression and increased apoptotic activity. Loss of Bcl-2 expression was strongly correlated with increased apoptotic and necrotic cell death, high proliferation rate and high tumour grade, supporting a model in which Bcl-2 not only mediates cell death, but also cell division in breast cancer tissue, and in which regulation of cell division and cell death are tightly linked.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Division
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, bcl-2*
  • Humans
  • Ki-67 Antigen / analysis
  • Necrosis
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Premenopause
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Receptors, Estrogen / analysis
  • bcl-2-Associated X Protein
  • bcl-X Protein


  • BAX protein, human
  • BCL2L1 protein, human
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen
  • bcl-2-Associated X Protein
  • bcl-X Protein