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

A high level of estrogen receptor-α (ER-α) is believed to be favorable in the prognosis and treatment of certain female cancers. ER-α expression in the ER-negative breast cancer cell lines inhibits their proliferation and invasive, metastatic potential in vitro. We stably overexpressed the ER-α in the human endometrial cancer cell line Ishikawa and showed that, unlike estradiol, high levels of ER-α significantly inhibit the growth of tumors xenografted from the Ishikawa cells. Subsequent to ER-α overexpression, in vivo down-regulation of vascular endothelial growth factor was observed in tumor xenografts. In addition, these tumors showed an inhibition of vascularization and of the angiogenic agent, integrin α_vβ₃. Involvement of a switch in the angiogenic pathways during tumorigenesis has been a recent focus of interest. Our results indicate that a high level of ER-α may be beneficial in the control of female cancers because of its inhibitory effect on such angiogenic pathways.