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
Main Authors: Kocić, Jelena, Villar, Victor, Krstić, Aleksandra, Santibanez, Juan F.
Format: Journal Article
Language:English
Published: 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.
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.
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  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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