Interaction between bcl-2 and p21 (WAF1/CIP1) in breast carcinomas with wild-type p53

Int J Cancer. 1997 Sep 26;73(1):38-41. doi: 10.1002/(sici)1097-0215(19970926)73:1<38::aid-ijc7>;2-2.


The bcl-2 protein is found to be over-expressed in many types of human tumours and is a potent inhibitor of apoptosis. The exact mechanism by which bcl-2 prevents apoptosis and exercises its oncogenic effect is still unclear. Other studies on cell lines have reported that bcl-2 over-expression is related to suppression of p21 (WAF1/CIP). We have investigated the relationship between bcl-2 protein over-expression and expression of the p21 protein in a series of human breast carcinomas. Selected tumour samples from 100 breast-cancer patients (38 with abnormal p53 status, scored as protein accumulation and/or mutation, and 62 without detectable p53 alterations), were immunostained for bcl-2 protein, the p21 protein and the oestrogen-receptor (ER) protein. A highly significant association was found between reduced p21-protein expression and over-expression of bcl-2 in tumours with no detectable p53 alterations (p < 0.001). A significant association was seen between ER immunoreactivity and expression of the bcl-2 protein, as well as between bcl-2 protein expression and tumours of the higher differentiation grade (grade-2 tumours). No association was seen between bcl-2 over-expression and the presence of metastases. Our findings indicate that down-regulation of p21 may be a result of up-regulation of bcl-2 independent of p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / analysis*
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / immunology


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen