Estrogen receptor-alpha in the inhibition of cancer growth and angiogenesis.
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.
Ali
S H
SH
Department of Biochemistry, Roswell Park Cancer Institute, State University of New York at Buffalo, USA. syedhali@hotmail.com
O'Donnell
A L
AL
Balu
D
D
Pohl
M B
MB
Seyler
M J
MJ
Mohamed
S
S
Mousa
S
S
Dandona
P
P
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
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