title: Estrogen receptor-alpha in the inhibition of cancer growth and angiogenesis.
abstract: A high level of estrogen receptor-alpha (ER-alpha) is believed to be favorable in the prognosis and treatment of certain female cancers. ER-alpha expression in the ER-negative breast cancer cell lines inhibits their proliferation and invasive, metastatic potential in vitro. We stably overexpressed the ER-alpha in the human endometrial cancer cell line Ishikawa and showed that, unlike estradiol, high levels of ER-alpha significantly inhibit the growth of tumors xenografted from the Ishikawa cells. Subsequent to ER-alpha 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 alphavbeta3. 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-alpha may be beneficial in the control of female cancers because of its inhibitory effect on such angiogenic pathways.
authors.affiliation: Department of Biochemistry, Roswell Park Cancer Institute, State University of New York at Buffalo, USA. syedhali@hotmail.com
authors.forename: S H
authors.initials: SH
authors.lastname: Ali
authors.forename: A L
authors.initials: AL
authors.lastname: O'Donnell
authors.forename: D
authors.initials: D
authors.lastname: Balu
authors.forename: M B
authors.initials: MB
authors.lastname: Pohl
authors.forename: M J
authors.initials: MJ
authors.lastname: Seyler
authors.forename: S
authors.initials: S
authors.lastname: Mohamed
authors.forename: S
authors.initials: S
authors.lastname: Mousa
authors.forename: P
authors.initials: P
authors.lastname: Dandona
mesh_terms: D000818:Animals; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism; D047628:Estrogen Receptor alpha; D005260:Female; D008024:Ligands; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011960:Receptors, Estrogen / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D047628:Estrogen Receptor alpha; D008024:Ligands; D008222:Lymphokines; D011960:Receptors, Estrogen; D019030:Receptors, Vitronectin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors