Role of p21 in prostaglandin A2-mediated cellular arrest and death.

Prostaglandin A2 (PGA2) treatment induces growth arrest of most cells, and we have recently shown that, for breast carcinoma MCF-7 cells, this is correlated with an induction of the cyclin-dependent kinase inhibitor p21 and reduced cyclin-dependent kinase 2 activity. In this study, we demonstrate that, in RKO cells, PGA2 treatment fails to induce growth arrest, but rather results in significant cell death. These effects are correlated with lack of p21 induction and enhanced cyclin-dependent kinase 2 activity. Reduction of endogenous p21 expression in MCF-7 cells through expression of antisense p21 resulted in a response pattern approaching that seen in RKO cells, characterized by diminished growth arrest and increased death. These findings support a role for p21 in PGA2-mediated growth arrest, which we propose serves to prevent cell death caused by inappropriate cell cycle progression.