We previously reported that 12-O-tetra-decanoylphorbol-13-acetate (TPA) induces microglia-like differentiation and decreases malignancy in human prostate cancer TSU-Pr1 cells. To investigate the mechanism underlying differentiation and decrease of 9 malignancy in TSU-Pr1 cells treated with TPA, we attempted to identify genes expressed differentially during the differentiation using differential display. We successfully detected plasminogen activator inhibitor type-2 (PAI-2) as one gene up-regulated by TPA treatment. The change in expression of PAI-2 by TPA was blocked by treatment with protein kinase C or mitogen-activated protein kinase inhibitors. We also found that secretion of PAI-2 protein was increased by TPA treatment. Moreover, we demonstrated that suppression of invasive activity of TSU-Prl cells by TPA treatment was blocked by co-treatment with anti-PAI-2 antibody. These results suggest that induction of PAI-2 is associated with suppression of invasive activity in TSU-Pr1 cells treated with TPA. (C) 2003 Elsevier Inc. All rights reserved.