[Inhibition of angiogenesis on the chicken chorioallantoic membrane by Ets 1 antisense oligodeoxyribonucleotides].

The Ets 1 transcription factor, the founder of the ets gene family of transcriptional regulators, has strongly been supposed to play a role in angiogenesis under both physiological and pathological conditions including tumor vascularization. An in vivo role has nevertheless not yet been proven. We therefore investigated whether an Ets 1 antisense oligodesoxynucleotide (ODN) blockade effectively inhibits in vivo angiogenesis in the chicken chorioallantois membrane-assay. We used a 20-mer phosphorothioate directed against the AUG initiation codon and a short 3' sequence of the c-ets 1 mRNA (5'-AGATCGACGGCCGCCTTCAT-3') in order to block Ets 1 expression. Three quantities of either antisense or negative control sense ODNs were directly applied on the chorioallantois membrane on day five of development and results evaluated on day seven. No effect on angiogenesis was seen in the antisense group treated with 2.5 micrograms ODN/egg compared to the sense control group. In contrast chorioallantoic blood vessel numbers and diameters were considerably reduced after application of 5 micrograms antisense ODN. 10 micrograms of either antisense or sense ODNs turned out to be toxic: all 6 embryos had died on day seven. Our results are the first proof that the Ets 1 transcription factor is actually necessary for the regulation of in vivo angiogenesis. Its role is probably not restricted to development but also concerns new blood vessel formation during chronic inflammation and tumor vascularization.