Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells

Abstract EN

Purpose.

To determine whether Ski-interacting protein (SKIP) regulates TGF-β1-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-β1 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-β1 treatment inhibited uPA production.

Both PAI-1 and MMP-9 production levels were increased in response to TGF-β1.

The ectopic expression of SKIP inhibited both TGF-β1-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-β1 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.