Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides.
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.
Chen
Z
Z
Scientific Applications International Corporation, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Fisher
R J
RJ
Riggs
C W
CW
Rhim
J S
JS
Lautenberger
J A
JA
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
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