Abstract
Ets-1 is a transcription factor regulating the expression of matrix-degrading proteinases and is believed to play a critical role in cell migration and tumor invasion. The aim of this study is to investigate the direct induction of ets-1 with consequential upregulation of collagenase-1 (MMP-1) by cell adhesion to extracellular matrix and to identify intracellular signal transduction pathways involved in ets-1 induction in cultured endothelial cells. The expressions of ets-1 mRNA and protein as well as MMP-1 protein were induced by cell adhesion to type I collagen and antisense ets-1 oligonucleotides impaired that MMP-1 expression. In addition, protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibitors abrogated their induction, showing the suppression of focal adhesion kinase phosphorylation. These results suggest that ets-1 induced by cell adhesion to extracellular matrix directly upregulates MMP-1 expression via PTK and PKC activation in cultured endothelial cells.
©2002 Elsevier Science (USA).
MeSH terms
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Animals
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Cattle
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Cell Adhesion / physiology
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Cells, Cultured
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Collagen Type I / metabolism
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Endothelin-1 / pharmacology
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Endothelium, Vascular / cytology
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Endothelium, Vascular / metabolism*
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Enzyme Inhibitors / pharmacology
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Extracellular Matrix / metabolism*
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Focal Adhesion Protein-Tyrosine Kinases
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Integrins / biosynthesis
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Intercellular Adhesion Molecule-1 / biosynthesis
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Matrix Metalloproteinase 1 / metabolism*
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Oligonucleotides, Antisense / pharmacology
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Phosphorylation / drug effects
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Protein Kinase C / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins / pharmacology
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Proto-Oncogene Proteins c-ets
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RNA, Messenger / biosynthesis
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Signal Transduction / physiology
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription Factors / pharmacology
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Up-Regulation
Substances
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Collagen Type I
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Endothelin-1
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Enzyme Inhibitors
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Integrins
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Oligonucleotides, Antisense
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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RNA, Messenger
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Transcription Factors
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Intercellular Adhesion Molecule-1
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Protein-Tyrosine Kinases
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Focal Adhesion Protein-Tyrosine Kinases
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Protein Kinase C
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Matrix Metalloproteinase 1
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Tetradecanoylphorbol Acetate