title: Interaction between bcl-2 and p21 (WAF1/CIP1) in breast carcinomas with wild-type p53.
abstract: 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.
authors.affiliation: Department of Genetics, Norwegian Radium Hospital, Montebello, Norway.
authors.forename: I K
authors.initials: IK
authors.lastname: Bukholm
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.forename: R
authors.initials: R
authors.lastname: Kåresen
authors.forename: U
authors.initials: U
authors.lastname: Jacobsen
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen-Dale
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis / Q000276:immunology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen