EXPERIMENTAL-MODELS OF ANGIOGENESIS TO ST UDY THE FUNCTION OF ETS1 TRANSCRIPTION FACTOR

The Ets1 transcription factor gene is expressed in endothelial cells d uring blood vessel formation under normal or pathological conditions. The proposed hypothesis aims to involve Ets1 in the regulation of angi ogenesis processes by activating the transcription of genes encoding m atrix-degrading proteases. In vivo experiments allowing specific manip ulation of Pts1 gene expression or activity within endothelial cells a re necessary to investigate the functional role of Ets1. Two experimen tal 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 develop ed in order to obtain transgenic mice expressing specifically in endot helial cells an ets1 transdominant negative mutant under the control o f the tek and lie promoters. These tools should allo cv interference w ith Ets1 activity at defined stages during normal or pathological deve lopment.