The Ets family contains transcriptional activators and repressors involvedin angiogenesis

The Ets family contains a growing number of transcriptional activators and inhibitors, which activity is regulated by phosphorylation and protein-prot ein interactions. Among these factors, Ets1, Erg1 and Fli1 are expressed in endothelial cells during angiogenesis in normal and pathological developme nt. The expression of these transcription factors is regulated by angiogeni c factors in cultured endothelial cells, as well as by various stresses occ urring during angiogenesis. Transfection experiments and transgenic mice an alysis revealed that Ets family members are involved in the transcriptional regulation of endothelial specific genes such as those encoding Tiel and - 2, VEGFR1 and -2 and VE-Cadherin. In vitro studies plead for a role of Ets family members in endothelial cell adhesion, spreading and motility. Gene i nactivation experiments show that Ets1 is dispensable for embryonic develop ment. The phenotype of knocked-out embryos indicates that Tel is required f or maintenance of the developing vascular network in the yolk sac. Altogeth er, we suggest that Ets family members act both positively and negatively d uring the different steps of the angiogenic process. The regulation of the initiation of gene transcription arises from the combined activity of diffe rent transcriptional regulators. Therefore very few transcription factors a re specific for a physiological process, or a given cell type. The transcri ptional network that regulates blood vessel formation involves transcriptio n factors which are expressed in a variety of situations. The Lung Kruppel Like Factor (LKLF) which is required for blood vessel stabilisation during murine development is also expressed in the primitive vertebrae and in the lung of the adult (C.T. Kuo, M.L. Veselits, K.P. Barton, M.M. Lu, C. Clende nin, J.M. Leiden, The LKLF transcription factor is required for normal tuni ca media formation and blood vessel stabilisation during murine embryogenes is, Genes Dev. 11 (22) (1997) 2996-3006). Scl/Tal1 which is essential for a ngiogenic remodelling of the yolk sac capillary network (J.E. Visvader, Y. Fujiwara, S.H. Orkin, Unsuspected role for the T-cell leukemia protein SCL/ tal-1 in vascular development, Genes Dev. 12 (4) (1998) 473-479), is involv ed in blood cell development and is also expressed in the developing brain. The EPAS transcription factor which was thought to be endothelial cell spe cific in the mouse embryo (H. Tian, S.L. McKnight, D.W. Russell, Endothelia l PAS domain protein 1 (EPAS1), a transcription factor selectively expresse d in endothelial cells, Genes Dev. 11 (1) (1997) 72-82) is also expressed i n the liver, kidney and cells of the sympathetic nervous system of the chic k embryo (J. Favier, H. Kempf, P. Corvol, J.M. Gasc, Cloning and expression pattern of EPAS1 in the chicken embryo. Colocalization with tyrosine hydro xylase, FEBS Lett. 462 (1-2) (1999) 19-24). Ets1, which expression was orig inally detected in lymphoid cells of adult tissues, has been the first tran scription factor to be identified in endothelial cells during angiogenesis in the embryo (B. Vandenbunder, L. Pardanaud, T. Jaffredo, M.A. Mirabel, D. Stehelin, Complementary patterns of expression of c-ets1, c-myb and c-myc in the blood-forming system of the chick embryo, Development 107 (1989) 265 -274) and in tumours (N. Wernert, M.B. Raes, P. Lassalle, M.P. Dehouck. B. Gosselin, B. Vandenbunder. D. Stehelin. The c-ets 1 proto-oncogene is a tra nscription factor expressed in endothelial cells during tumor vascularisati on and other forms of angiogenesis in man, Am. J. Path. 140 (1992) 119-127) . Since then, the Ets family has extended and this review will emphasise th e relationships between these factors and angiogenesis. (C) 2001 Elsevier Science Ltd. All rights reserved.