In vitro regulation of vascular endothelial growth factor by estrogens and antiestrogens in estrogen-receptor positive breast cancer.
BACKGROUND
The effects of antiestrogens on angiogenesis in breast cancer are not fully defined. In this study we investigated the in vitro effects of antiestrogens at different concentrations on vascular endothelial growth factor (VEGF) production in estrogen receptor (ER)-positive breast cancer cells.


METHODS
The dose-dependent effects of 17beta-estradiol (E2), 4-hydroxytamoxifen (4OHT), and ICI182,780 were analyzed both with reference to growth rates and VEGF protein production using enzyme-linked immunosorbent assay (ELISA) in MCF-7 cells.


RESULTS
E2 stimulated both the growth rates and VEGF production of MCF-7 cells in the same manner. Although 4OHT stimulated the growth rates as an agonistic effect in an estrogen-free media at levels ranging from 1 nM to 1 micro M, it did not stimulate VEGF expression at the same levels except for at 1 micro M. Although 4OHT had a weak agonistic effect on VEGF production at 1 micro M in an estrogen-free media, it significantly inhibited E2-stimulated VEGF production at the same level. A cytotoxic effect was observed with 10 micro M 4OHT that paradoxically caused a prominent increase in VEGF production. ICI182,780 had no significant effects on the growth rates or VEGF production in this cell line.


CONCLUSIONS
These results support the hypothesis that tamoxifen could inhibit angiogenesis induced by estrogens in ER-positive breast cancer cells.
Northwestern University Medical School, Robert H. Lurie Comprehensive Cancer Center, USA. QYQ05440@nifty.ne.jp
Hiroyuki
H
Takei
Eun-Sook
ES
Lee
V Craig
VC
Jordan
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008222:Lymphokines / Q000187:drug effects* / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D016228:Endothelial Growth Factors; D004965:Estrogen Antagonists; D008222:Lymphokines; D011960:Receptors, Estrogen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; D004958:Estradiol