SKIP Downregulation Increases TGF- β 1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes
Transforming growth factor-beta (TGF- β 1) 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- β 1 signal transduction, but its role in the induction of cell malignance by TGF- β 1 has not...
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Published in: | Scientifica (Cairo) Vol. 2012; pp. 1 - 8 |
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2012
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Abstract | Transforming growth factor-beta (TGF-
β
1) 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-
β
1 signal transduction, but its role in the induction of cell malignance by TGF-
β
1 has not been fully elucidated so far. In the present study, we analyzed the role of SKIP on TGF-
β
1-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-
β
1 treatment. The downregulation of SKIP produced an enhancement in TGF-
β
1-activated ERK1,2 MAP kinase as well as increased transactivation of downstream Elk1 transcription factor. The increased MMP-9 production in response to TGF-
β
1 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-
β
1-induced MMP-9 expression acting by controlling ERK1,2 signaling in transformed cells. |
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AbstractList | Transforming growth factor-beta (TGF-
β
1) 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-
β
1 signal transduction, but its role in the induction of cell malignance by TGF-
β
1 has not been fully elucidated so far. In the present study, we analyzed the role of SKIP on TGF-
β
1-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-
β
1 treatment. The downregulation of SKIP produced an enhancement in TGF-
β
1-activated ERK1,2 MAP kinase as well as increased transactivation of downstream Elk1 transcription factor. The increased MMP-9 production in response to TGF-
β
1 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-
β
1-induced MMP-9 expression acting by controlling ERK1,2 signaling in transformed cells. |
Author | Krstić, Aleksandra Kocić, Jelena Villar, Victor Santibanez, Juan F. |
Author_xml | – sequence: 1 givenname: Jelena surname: Kocić fullname: Kocić, Jelena organization: Laboratory for Experimental Hematology, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, P.O. Box 102, 11129 Belgrade, Serbia, Department of Biology, University of the Balearic Islands, Ctrretera Valldemossa, Km 7.5, 07122 Palma de Mallorca, Spain – sequence: 2 givenname: Victor surname: Villar fullname: Villar, Victor organization: Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile – sequence: 3 givenname: Aleksandra surname: Krstić fullname: Krstić, Aleksandra organization: Laboratory for Experimental Hematology, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, P.O. Box 102, 11129 Belgrade, Serbia – sequence: 4 givenname: Juan F. surname: Santibanez fullname: Santibanez, Juan F. organization: Laboratory for Experimental Hematology, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, P.O. Box 102, 11129 Belgrade, Serbia, Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile |
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Snippet | Transforming growth factor-beta (TGF-
β
1) is a potent inductor of matrix metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting protein... |
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Title | SKIP Downregulation Increases TGF- β 1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes |
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