Foxs and Ets in the transcriptional regulation of endothelial cell differentiation and angiogenesis

During tumour growth the surrounding vasculature forms new vessels which penetrate into the stroma and bring oxygen and nutrients to the proliferating cancer cells. The ability to control and reduce this phenomenon may have important therapeutic implications. Angiogenesis is a complex event which requires endothelial cell sprouting, lumen formation, tubulogenesis and is regulated by the coordinated action of different transcription factors. Studies on promoters of endothelial cell-specific genes or gene inactivation experiments reveal the extreme complexity of the system. Many transcription factors are implicated in vascular development and the majority are not endothelial-specific. Their interaction leads to endothelial cell differentiation and acquisition of arterial, venous and lymphatic properties. Two large families of transcription factors, Foxs and Ets, play a major role in these events. They participate in both embryonic and adult angiogenesis. The FoxO subgroup regulates the correct organization of the vascular system, controlling excessive endothelial growth and inducing apoptosis both in embryos and adult mice. Ets factors participate in early endothelial differentiation and angiogenesis. Many members of this family are expressed very early in the developing vasculature and Ets consensus binding domains are present in essentially all endothelial cell-specific gene promoters. In this review we discuss the overall transcriptional regulation of vascular development with a particular focus on some specific members of these two families considered important in the formation and maintenance of the vascular network.