SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes
Transforming growth factor-beta (TGF-β1) is a potent inductor of matrix metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting protein (SKIP) has been described as a regulator of TGF-β1 signal transduction, but its role in the induction of cell malignance by TGF-β1 has not been...
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| Language: | English |
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Wiley
2012-01-01
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| Series: | Scientifica |
| Online Access: | http://dx.doi.org/10.6064/2012/861647 |
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| author | Jelena Kocić Victor Villar Aleksandra Krstić Juan F. Santibanez |
| author_facet | Jelena Kocić Victor Villar Aleksandra Krstić Juan F. Santibanez |
| author_sort | Jelena Kocić |
| collection | DOAJ |
| description | Transforming growth factor-beta (TGF-β1) is a potent inductor of matrix metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting protein (SKIP) has been described as a regulator of TGF-β1 signal transduction, but its role in the induction of cell malignance by TGF-β1 has not been fully elucidated so far. In the present study, we analyzed the role of SKIP on TGF-β1-induced MMP-9 production. Mouse transformed keratinocytes (PDV) were stably transfected with SKIP antisense construct. We observed that SKIP depletion provoked an enhancement in the expression of MMP-9 in response to TGF-β1 treatment. The downregulation of SKIP produced an enhancement in TGF-β1-activated ERK1,2 MAP kinase as well as increased transactivation of downstream Elk1 transcription factor. The increased MMP-9 production in response to TGF-β1 was dependent of MAPK activation as PD98059, an MEK inhibitor, reduced MMP-9 expression in SKIP antisense transfected cells. Thus, we propose SKIP as a regulatory protein in TGF-β1-induced MMP-9 expression acting by controlling ERK1,2 signaling in transformed cells. |
| format | Article |
| id | doaj-art-d1269113e45c40dbb9d3e8f40b935251 |
| institution | Kabale University |
| issn | 2090-908X |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
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| series | Scientifica |
| spelling | doaj-art-d1269113e45c40dbb9d3e8f40b9352512025-02-03T01:33:07ZengWileyScientifica2090-908X2012-01-01201210.6064/2012/861647861647SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed KeratinocytesJelena Kocić0Victor Villar1Aleksandra Krstić2Juan F. Santibanez3Laboratory for Experimental Hematology, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, P.O. Box 102, 11129 Belgrade, SerbiaLaboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, ChileLaboratory for Experimental Hematology, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, P.O. Box 102, 11129 Belgrade, SerbiaLaboratory for Experimental Hematology, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, P.O. Box 102, 11129 Belgrade, SerbiaTransforming growth factor-beta (TGF-β1) is a potent inductor of matrix metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting protein (SKIP) has been described as a regulator of TGF-β1 signal transduction, but its role in the induction of cell malignance by TGF-β1 has not been fully elucidated so far. In the present study, we analyzed the role of SKIP on TGF-β1-induced MMP-9 production. Mouse transformed keratinocytes (PDV) were stably transfected with SKIP antisense construct. We observed that SKIP depletion provoked an enhancement in the expression of MMP-9 in response to TGF-β1 treatment. The downregulation of SKIP produced an enhancement in TGF-β1-activated ERK1,2 MAP kinase as well as increased transactivation of downstream Elk1 transcription factor. The increased MMP-9 production in response to TGF-β1 was dependent of MAPK activation as PD98059, an MEK inhibitor, reduced MMP-9 expression in SKIP antisense transfected cells. Thus, we propose SKIP as a regulatory protein in TGF-β1-induced MMP-9 expression acting by controlling ERK1,2 signaling in transformed cells.http://dx.doi.org/10.6064/2012/861647 |
| spellingShingle | Jelena Kocić Victor Villar Aleksandra Krstić Juan F. Santibanez SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes Scientifica |
| title | SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes |
| title_full | SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes |
| title_fullStr | SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes |
| title_full_unstemmed | SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes |
| title_short | SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes |
| title_sort | skip downregulation increases tgf β1 induced matrix metalloproteinase 9 production in transformed keratinocytes |
| url | http://dx.doi.org/10.6064/2012/861647 |
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