Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells
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 p...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Prostate Cancer |
| Online Access: | http://dx.doi.org/10.1155/2013/398253 |
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| _version_ | 1832556176938631168 |
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| author | Victor Villar Jelena Kocic Juan F. Santibanez |
| author_facet | Victor Villar Jelena Kocic Juan F. Santibanez |
| author_sort | Victor Villar |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-342afe2e89774a8891ecf6b460f7c70a |
| institution | Kabale University |
| issn | 2090-3111 2090-312X |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Prostate Cancer |
| spelling | doaj-art-342afe2e89774a8891ecf6b460f7c70a2025-02-03T05:46:01ZengWileyProstate Cancer2090-31112090-312X2013-01-01201310.1155/2013/398253398253Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer CellsVictor Villar0Jelena Kocic1Juan F. Santibanez2Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, 7810000 Santiago, ChileLaboratory for Experimental Haematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotica 4, P.O. Box 102, 11129 Belgrade, SerbiaLaboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, 7810000 Santiago, ChilePurpose. 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.http://dx.doi.org/10.1155/2013/398253 |
| spellingShingle | Victor Villar Jelena Kocic Juan F. Santibanez Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells Prostate Cancer |
| title | Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells |
| title_full | Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells |
| title_fullStr | Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells |
| title_full_unstemmed | Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells |
| title_short | Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells |
| title_sort | skip regulates tgf β1 induced extracellular matrix degrading proteases expression in human pc 3 prostate cancer cells |
| url | http://dx.doi.org/10.1155/2013/398253 |
| work_keys_str_mv | AT victorvillar skipregulatestgfb1inducedextracellularmatrixdegradingproteasesexpressioninhumanpc3prostatecancercells AT jelenakocic skipregulatestgfb1inducedextracellularmatrixdegradingproteasesexpressioninhumanpc3prostatecancercells AT juanfsantibanez skipregulatestgfb1inducedextracellularmatrixdegradingproteasesexpressioninhumanpc3prostatecancercells |