title: Skip Regulates TGF- β 1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells.
abstract: Purpose. To determine whether Ski-interacting protein (SKIP) regulates TGF- β 1-stimulated expression of urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and uPA Inhibitor (PAI-1) in the androgen-independent human prostate cancer cell model. Materials and Methods. PC-3 prostate cancer cell line was used. The role of SKIP was evaluated using synthetic small interference RNA (siRNA) compounds. The expression of uPA, MMP-9, and PAI-1 was evaluated by zymography assays, RT-PCR, and promoter transactivation analysis. Results. In PC-3 cells TGF- β 1 treatment stimulated uPA, PAI-1, and MMP-9 expressions. The knockdown of SKIP in PC-3 cells enhanced the basal level of uPA, and TGF- β 1 treatment inhibited uPA production. Both PAI-1 and MMP-9 production levels were increased in response to TGF- β 1. The ectopic expression of SKIP inhibited both TGF- β 1-induced uPA and MMP-9 promoter transactivation, while PAI-1 promoter response to the factor was unaffected. Conclusions. SKIP regulates the expression of uPA, PAI-1, and MMP-9 stimulated by TGF- β 1 in PC-3 cells. Thus, SKIP is implicated in the regulation of extracellular matrix degradation and can therefore be suggested as a novel therapeutic target in prostate cancer treatment.
authors.affiliation: Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, 7810000 Santiago, Chile ; Department of Biology, University of the Balearic Islands, Ctra Valldemossa, Km 7.5 , 07122 Palma de Mallorca, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Villar
authors.forename: Jelena
authors.initials: J
authors.lastname: Kocic
authors.forename: Juan F
authors.initials: JF
authors.lastname: Santibanez