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. Method: The dose-dependent effects of 17β-estradiol (E2), 4-hydroxytamoxifen (40HT), and 10182,780 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 40HT stimulated the growth rates as an agonistic effect in an estrogen-free media at levels ranging from 1 nM to 1 μM, it did not stimulate VEGF expression at the same levels except for at 1 μM. Although 40HT had a weak agonistic effect on VEGF production at 1 μM in an estrogen-free media, it significantly inhibited Erftimulated VEGF production at the same level. A cytotoxic effect was observed with 10 μM 40HT 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.