Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides
Chen, Z.; Fisher, R.J.; Riggs, C.W.; Rhim, J.S.; Lautenberger, J.A.
Cancer Research 57(10): 2013-2019
1997
ISSN/ISBN: 0008-5472 PMID: 9157999 Document Number: 478900
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.