Estrogen receptor-alpha in the inhibition of cancer growth and angiogenesis

A high level of estrogen receptor-alpha (ER-alpha) is believed to be favora ble in the prognosis and treatment of certain female cancers. ER-alpha expr ession in the ER-negative breast cancer cell lines inhibits their prolifera tion and invasive, metastatic potential in vitro. We stably overexpressed t he ER-alpha in the human endometrial cancer cell line Ishikawa and showed t hat, unlike estradiol, high levels of ER-alpha significantly inhibit the gr owth of tumors xenografted from the Ishikawa cells. Subsequent to ER-alpha overexpression, in vivo down-regulation of vascular endothelial growth fact or was observed in tumor xenografts. In addition, these tumors showed an in hibition of vascularization and of the angiogenic agent, integrin alpha (v) beta (3). Involvement of a switch in the angiogenic pathways during tumorig enesis has been a recent focus of interest. Our results indicate that a hig h level of ER-alpha may be beneficial in the control of female cancers beca use of its inhibitory effect on such angiogenic pathways.