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

Breast Cancer ◽  
2002 ◽  
Vol 9 (1) ◽  
pp. 39-42 ◽  
Author(s):  
Hiroyuki Takei ◽  
Eun-Sook Lee ◽  
V. Craig Jordan
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Estrogen Receptor Positive ◽  
Endothelial Growth Factor ◽  
Positive Breast Cancer

scholarly journals Xenoestrogens modulate vascular endothelial growth factor secretion in breast cancer cells through an estrogen receptor-dependent mechanism

2007 ◽  
Vol 196 (2) ◽  
pp. 399-412 ◽  
Author(s):  
Hélène Buteau-Lozano ◽  
Guillaume Velasco ◽  
Monique Cristofari ◽  
Patrick Balaguer ◽  
Martine Perrot-Applanat
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Breast Cancer Cells ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor ◽  
Dependent Mechanism ◽  
Mcf 7

Environmental chemicals may affect human health by disrupting endocrine function. Their possible role in the mammary gland and breast tumors is still unknown. Previous studies have demonstrated that vascular endothelial growth factor (VEGF), a key factor in angiogenesis and tumor progression, is an estrogen-regulated gene. We analyzed whether VEGF expression is regulated by different xenoestrogens in several breast cancer cells, MELN (derived from MCF-7) and MELP (derived from MDA-MB-231) and stably expressing estrogen receptor α (ERα); these cell lines stably express estrogen response element (β-globin)-luciferase. Genistein, bisphenol A (BPA), 4-(tert-octyl)phenol (OP), dieldrin, and several phthalates, including benzyl butyl phthalate (BBP) and di-ethyl-2-hexyle phthalate (DEHP), were first shown to be estrogenic. These compounds induced a dose-dependent increase of VEGF secretion in MELN and MCF-7 cells; maximal effect was observed at 1–10 μM non-cytotoxic concentrations and was inhibited by the antiestrogen ICI 182 780. VEGF increase was not observed in ERα-negative MDA-MB-231 cells. Most substances increased VEGF transcript levels in MELN cells. In contrast, γ-hexachlorocyclohexane, vinclozolin, and the phthalates (mono-n-butyl ester phthalic acid, di-isononyle phthalate, and di-isodecyle phthalate) were ineffective on both VEGF secretion and estrogenic luciferase induction in these cell lines. Specific kinase inhibitors PD98059, SB203580, or LY294002 suppressed the xenoestrogen-induced VEGF response, suggesting activation of MEK, p38 kinase, and phosphatidylinositol-3-kinase pathways. Our in vitro results show for the first time that genistein and xenoestrogens (BPA, OP, dieldrin, BBP, and DEHP at high concentrations) up-regulate VEGF expression in MELN cells by an ER-dependent mechanism. Since VEGF increases capillary permeability and breast tumor angiogenesis in vivo, the physiological relevance of these findings is discussed.

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