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In vitro regulation of vascular endothelial growth factor by estrogens and antiestrogens in estrogen-receptor positive breast cancer

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Abstract

Background

The effects of antiestrogens on angiogenesis in breast cancer are not fully defined. In this study we investigated thein 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 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 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.

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Abbreviations

VEGF:

Vascular endothelial growth factor

ER:

Estrogen receptor

E2 :

17β-Estradiol

40HT:

4-Hydroxytamoxifen

ELISA:

Enzyme-linked immunosorbent assay

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Authors and Affiliations

  1. Northwestern University Medical School, Robert H. Lurie Comprehensive Cancer Center, USA

    Hiroyuki Takei, Eun-Sook Lee & V. Craig Jordan

  2. Second Department of Surgery, Gunma University Faculty of Medicine, Japan

    Hiroyuki Takei

  3. Center for Breast Cancer, National Cancer Center, Korea

    Eun-Sook Lee

Authors
  1. Hiroyuki Takei
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  2. Eun-Sook Lee
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  3. V. Craig Jordan
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Corresponding authors

Correspondence to Hiroyuki Takei, Eun-Sook Lee or V. Craig Jordan.

Additional information

Reprint requests to Hiroyuki Takei, Second Department of Surgery, Gunma University Faculty of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.

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Takei, H., Lee, ES. & Craig Jordan, V. In vitro regulation of vascular endothelial growth factor by estrogens and antiestrogens in estrogen-receptor positive breast cancer. Breast Cancer 9, 39–42 (2002). https://doi.org/10.1007/BF02967545

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  • DOI: https://doi.org/10.1007/BF02967545

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