Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides

• Published in: Cancer research (Chicago, Ill.) Ill.), 1997-05, Vol.57 (10), p.2013-2019
• Main Authors: CHEN, Z.-Q, FISHER, R. J, RIGGS, C. W, RHIM, J. S, LAUTENBERGER, J. A
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Division - drug effects; Cell Movement - drug effects; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cells, Cultured; Collagen; Drug Combinations; Endothelial Growth Factors - antagonists & inhibitors; Endothelial Growth Factors - pharmacology; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Fundamental and applied biological sciences. Psychology; Gelatin; Gene Expression - drug effects; Gene Expression Regulation - drug effects; Humans; Laminin; Lymphokines - antagonists & inhibitors; Lymphokines - pharmacology; Membranes; Molecular and cellular biology; Oligonucleotides, Antisense - pharmacology; Proteoglycans; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-ets; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stimulation, Chemical; Tetradecanoylphorbol Acetate - pharmacology; Transcription Factors - biosynthesis; Transcription Factors - genetics; Urokinase-Type Plasminogen Activator - drug effects; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0008-5472; 1538-7445

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.