Stable over-expression of estrogen receptor-alpha in ECV304 cells inhibitsproliferation and levels of secreted endothelin-1 and vascular endothelialgrowth factor

Studies with mammalian vascular cells have suggested growth inhibitory effe cts of estrogen on the vascular wall. To investigate the involvement of est rogen receptor-alpha (ER) in the control of endothelial cell proliferation, we have stably transfected human estrogen receptor-alpha cDNA into the end othelial cell line ECV304. The clone ECV-ER, thus obtained, over-expresses estrogen receptor to a level similar to 10-fold higher than the parent cell line. Effects of this over-expression were studied on the cell growth rate , and on the levels of secreted endothelin-l and vascular endothelial growt h factor (VEGF). Similar to the previously reported data in other cell type s, we found the transfection of ER in ECV304 cells to be inhibitory to thei r growth. Our ER-over-expressing clone of ECV304 also showed an inhibition of secreted endothelin-l and VEGF levels. Moreover, the growth inhibition o f this ER-over-expressing clone was reversed by the addition of endothelin- l or VEGF to the medium. In view of the growth-stimulatory effect of endoth elin-l and VEGF on vascular cells, our results indicate that estrogen recep tor-alpha may bring about its growth inhibition partly by suppressing endot helin-l and/or VEGF production in ECV304 cells. (C) 1999 Published by Elsev ier Science Ireland Ltd. All rights reserved.