p53 regulates the expression of the tumor suppressor gene maspin

Maspin has been shown to inhibit tumor cell invasion and metastasis in brea st tumor cells. Maspin expression was detected in normal breast and prostat e epithelial cells, whereas tumor cells exhibited reduced or no expression. However, the regulatory mechanism of maspin expression remains unknown. We report here a rapid and robust induction of maspin expression in prostate cancer cells (LNCaP, DU145, and PC3) and breast tumor cells (MCF7) followin g wild type p53 expression from an adenovirus p53 expression vector (AdWTp5 3). p53 activates the maspin promoter by binding directly to the p53 consen sus-binding site present in the maspin promoter. DNA-damaging agents and cy totoxic drugs induced endogenous maspin expression in cells containing the wild type p53, Maspin expression was refractory to the DNA-damaging agents in cells containing mutant p53, These results, combined with recent studies of the tumor metastasis suppressor gene KAI1 and plasminogen activator inh ibitor 1 (PAI1), define a new category of molecular targets of p53 that hav e the potential to negatively regulate tumor invasion and/or metastasis.