[Experimental models of angiogenesis for the study of the Ets1 transcription factor]

The Ets1 transcription factor gene is expressed in endothelial cells during blood vessel formation under normal or pathological conditions. The proposed hypothesis aims to involve Ets1 in the regulation of angiogenesis processes by activating the transcription of genes encoding matrix-degrading proteases. In vivo experiments allowing specific manipulation of ets1 gene expression or activity within endothelial cells are necessary to investigate the functional role of Ets1. Two experimental models using retroviruses expressing ets1 mutants have been chosen: Chicken embryo development and tumour-induced angiogenesis in mice. Another approach targeted on the vascular endothelium has been developed in order to obtain transgenic mice expressing specifically in endothelial cells an ets1 transdominant negative mutant under the control of the tek and tie promoters. These tools should allow interference with Ets1 activity at defined stages during normal or pathological development.