Overexpression of p21(WAF1)/(CIPI) induces cell differentiation and growth inhibition in a human glioma cell line

Abstract

p21(WAFIICIPI) is a downstream mediator of p53 and mediates growth arrest by inhibiting the action of G1 cyclin-dependent kinases. Since cellular differentiation is frequently characterized by G1 arrest, we examined whether p21(WAFIICIPI) overexpression would induce growth suppression and differentiation in p53-defective human glioma cells. Overexpression of p21(WFIICIPI) resulted in an accumulation of cells in G1, altered morphology, growth arrest and cell differentiation. The extent of cell differentiation correlated with the level of p21(WAFIICIPI) as well as of proliferating cell nuclear antigen, cyclin E, and cdk 2, which associates with p21(WAFIICIPI). Our data suggest that gene transfer of p21(WAFIICIPI may arrest glioma cell growth in vivo by committing malignant glioma cells to a pathway of terminal differentiation.