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Adenoviral EGR-1 expression to inhibit angiogenesis and tumor growth

A n important finding during the course of this project was that adenoviral EGR-1 overexpression caused a reduced responsiveness of endothelial cells to growth factors, prevented sprouting and tubule formation in vitro and prolonged expression triggered apoptosis. Furthermore, EGR-1 expressing viruses completely inhibited cell invasion and vessel formation in the murine Matrigel model and resulted in a dramatic blockade of tumor growth in a murine fibrosarcoma model.

An analysis of this phenomenon showed that that EGR-1 can actually promote two different activities, one pro-proliferative and pro-angiogenic when expressed at low growth factor-induced level, and an anti-proliferative, anti-angiogenic and pro-apoptotic when overexpressed in a sustained way following infection with recombinant adenoviruses.

Obviously, overexpression of EGR-1 causes the preferential induction of potent feed-back inhibitory mechanisms resulting in inhibition of angiogenesis. This could be likely caused by differential modification of EGR-1 when expressed following growth factor stimulation or following adenoviral expression (acetylation versus phosphorylation).

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