Downregulation of the urokinase-type plasminogen activator receptor through inhibition of translation by antisense oligonucleotide suppresses invasion of human glioblastoma cells

We previously showed that downregulation of the urokinase-type plasminogen activator receptor (uPAR) in the SNB19 human glioblastoma cell line by the stable transfection of a plasmid expressing a 300 bp antisense sequence to the 5′ end of the uPAR gene produced a decrease in the amount of target mRNA. In a more recent study, we found that adenovirus-mediated transduction (Ad-uPAR) of the same uPAR antisense gene construct in SNB19 cells also downregulated uPAR protein levels. We report here that Ad-uPAR-transfected SNB19 cells produced the same amounts of target uPAR mRNA but significantly less protein by in vitro translation and by in situ [³⁵S] labeling compared to Ad-CMV vector-transfected and mock-transfected cells. This antisense construct also inhibited glioblastoma cell invasion confirming previous results. We conclude that downregulation of uPAR by this antisense gene construct results from inhibition of protein translation. This revised version was published online in July 2006 with corrections to the Cover Date.