Abstract
Vascular endothelial growth factor (VEGF) increased the level of ETS1 mRNA in human umbilical vein endothelial cells (HUVEC) and human lung microvascular endothelial cells (HMVEC-L) over 5-fold. Protein levels were shown to increase concordantly. VEGF was also found to stimulate the invasiveness of endothelial cells as measured by migration through Matrigel- or gelatin-coated membranes. The VEGF-induced invasiveness was inhibited by ETS1 antisense oligonucleotides but not by a sense control. In addition, the ETS1 antisense oligonucleotides reduced the levels of ETS1 and urokinase-type plasminogen activator mRNAs. The antisense oligonucleotides directed against the ETS1 gene thus altered a cellular property of endothelial cells that is correlated with the ability of the cells to migrate through basement membranes. Together, these observations demonstrate a direct role for the ETS1 gene in angiogenesis.
MeSH terms
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Cell Division / drug effects
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Cell Movement / drug effects
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Cells, Cultured
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Collagen
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Drug Combinations
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Endothelial Growth Factors / antagonists & inhibitors*
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Endothelial Growth Factors / pharmacology*
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Endothelium, Vascular / cytology*
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Endothelium, Vascular / drug effects*
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Gelatin
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Gene Expression / drug effects
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Gene Expression Regulation / drug effects
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Humans
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Laminin
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Lymphokines / antagonists & inhibitors*
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Lymphokines / pharmacology*
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Membranes
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Oligonucleotides, Antisense / pharmacology*
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Proteoglycans
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins c-ets
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Stimulation, Chemical
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factors / biosynthesis
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Transcription Factors / genetics*
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Urokinase-Type Plasminogen Activator / drug effects
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Drug Combinations
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ETS1 protein, human
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Endothelial Growth Factors
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Laminin
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Lymphokines
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Oligonucleotides, Antisense
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Proteoglycans
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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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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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matrigel
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Gelatin
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Collagen
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Urokinase-Type Plasminogen Activator
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Tetradecanoylphorbol Acetate