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...

Full description

Saved in:
Bibliographic Details
Main Authors: Jelena Kocić, Victor Villar, Aleksandra Krstić, Juan F. Santibanez
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Scientifica
Online Access:http://dx.doi.org/10.6064/2012/861647
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832558202855620608
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
record_format Article
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
work_keys_str_mv AT jelenakocic skipdownregulationincreasestgfb1inducedmatrixmetalloproteinase9productionintransformedkeratinocytes
AT victorvillar skipdownregulationincreasestgfb1inducedmatrixmetalloproteinase9productionintransformedkeratinocytes
AT aleksandrakrstic skipdownregulationincreasestgfb1inducedmatrixmetalloproteinase9productionintransformedkeratinocytes
AT juanfsantibanez skipdownregulationincreasestgfb1inducedmatrixmetalloproteinase9productionintransformedkeratinocytes