title: Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides.
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.
authors.affiliation: Scientific Applications International Corporation, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: R J
authors.initials: RJ
authors.lastname: Fisher
authors.forename: C W
authors.initials: CW
authors.lastname: Riggs
authors.forename: J S
authors.initials: JS
authors.lastname: Rhim
authors.forename: J A
authors.initials: JA
authors.lastname: Lautenberger
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D005780:Gelatin; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007797:Laminin; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008566:Membranes; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011509:Proteoglycans; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D004338:Drug Combinations; C494041:ETS1 protein, human; D016228:Endothelial Growth Factors; D007797:Laminin; D008222:Lymphokines; D016376:Oligonucleotides, Antisense; D011509:Proteoglycans; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C059485:matrigel; D005780:Gelatin; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate