INTERACTION BETWEEN BCL-2 AND P21 (WAF1 CIP1) IN BREAST CARCINOMAS WITH WILD-TYPE P53/

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 b y which bcl-2 prevents apoptosis and exercises its oncogenic effect is still unclear. Other studies on cell lines have reported that bcl-2 o ver-expression is related to suppression of p21 (WAFI/CIP). We have in vestigated the relationship between bcl-2 protein overexpression and e xpression of the p21 protein in a series of human breast carcinomas, S elected tumour samples from 100 breast-cancer patients (38 with abnorm al p53 status, scored as protein accumulation and/or mutation, and 62 without detectable p53 alterations), were immunostained for bcl-2 prot ein, the p21 protein and the oestrogen-receptor (ER) protein, A highly significant association was found between reduced p21-protein express ion and over-expression of bcl-2 in tumours with no detectable p53 alt erations (p < 0.001). A significant association was seen between ER im munoreactivity and expression of the bcl-2 protein, as well as between bcl-2 protein expression and tumours of the higher differentiation gr ade (grade-2 tumours). Mo association was seen between bcl-2 over-expr ession and the presence of metastases. Our findings indicate that down -regulation of p21 may be a result of up-regulation of bcl-2 independe nt of p53. (C) 1997 Wiley-Liss Inc.