OVEREXPRESSION OF P21(WAF1 CIP1) INDUCES GROWTH ARREST, GIANT-CELL FORMATION AND APOPTOSIS IN HUMAN BREAST-CARCINOMA CELL-LINES/

The p21(WAF1/CIP1) protein was shown to be a critical downstream effec tor of p53 and a potent inhibitor of cyclin-dependent kinases. We inve stigated the effects of exogenous p21(WAF1/CIP1) in two different huma n breast carcinoma (HBC) cell lines MCF-7 and T47D, p21(WAF1/CIP1) tra nsfected cells formed significantly reduced number of drug-resistant c olonies than their mock-transfected counterparts, The majority of the p21(WAF1/CIP1) transfected MCF-7 cells acquired 50-100-fold increase i n their sizes and persisted as single giant cells for several days wit hout cell division, while the remainder underwent nuclear division (mu ltiple nuclei) but were unable to complete cytokinesis, and finally al l succumbed to apoptosis, Only few p21(WAF1/CIP1) transfected T47D cel ls displayed increase in their sizes while a number of them formed sma ll sized drug-resistant colonies which diminished in size due to cell death, The cells in these shrinking colonies exhibited characteristic signs of apoptosis such as chromatin condensation and fragmented nucle i while their membrane integrity was preserved, Thus in HBC cell lines the growth suppression due to enforced overexpression of p21(WAF1/CIP 1) is associated with giant cell formation and apoptosis.