Stable over-expression of estrogen receptor-alpha in ECV304 cells inhibits proliferation and levels of secreted endothelin-1 and vascular endothelial growth factor.
Studies with mammalian vascular cells have suggested growth inhibitory effects of estrogen on the vascular wall. To investigate the involvement of estrogen receptor-alpha (ER) in the control of endothelial cell proliferation, we have stably transfected human estrogen receptor-alpha cDNA into the endothelial cell line ECV304. The clone ECV-ER, thus obtained, over-expresses estrogen receptor to a level approximately 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-1 and vascular endothelial growth factor (VEGF). Similar to the previously reported data in other cell types, we found the transfection of ER in ECV304 cells to be inhibitory to their growth. Our ER-over-expressing clone of ECV304 also showed an inhibition of secreted endothelin-1 and VEGF levels. Moreover, the growth inhibition of this ER-over-expressing clone was reversed by the addition of endothelin-1 or VEGF to the medium. In view of the growth-stimulatory effect of endothelin-1 and VEGF on vascular cells, our results indicate that estrogen receptor-alpha may bring about its growth inhibition partly by suppressing endothelin-1 and/or VEGF production in ECV304 cells.
Ali
S H
SH
Diabetes-Endocrine Centre of Western New York, CGF Health System, State University of New York at Buffalo, 14209, USA.
O'Donnell
A L
AL
Mohamed
S
S
Mousa
S
S
Dandona
P
P
D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha; D005786:Gene Expression Regulation; D006801:Humans; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D019332:Endothelin-1; D047628:Estrogen Receptor alpha; D008222:Lymphokines; D011960:Receptors, Estrogen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors