High levels of oestrogen receptor-alpha in tumorigenesis: inhibition of cell growth and angiogenic factors

We previously found that the stable overexpression of oestrogen receptor-al pha in the human endothelial cell line ECV304* inhibits its growth in vitro , and that this inhibition is possibly mediated through a down-regulation o f the vasoactive agents endothelin-1 and vascular endothelial growth factor . Here we show an in vivo growth-inhibitory effect of oestrogen receptor-al pha overexpression in tumours initiated in nude mice from the same clone of ECV304. In addition, we show that this growth inhibition is accompanied by an alpha (v)beta (3)-mediated inhibition of cell migration in vitro, and a downregulation of the integrin alpha (v)beta (3) vascular endothelial grow th factor and vascularization in vivo. The levels of vascular endothelial g rowth factor and integrin alpha (v)beta (3) through their effect on cell gr owth and migration, contribute to the process of angiogenesis and to the pa thogenesis of atherosclerosis and cancer. The results shown here demonstrat e that a higher level of oestrogen receptor-alpha in the cell, through its effect on certain angiogenic factors, may play a role in the control of ang iogenesis.