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Vascular Endothelial Growth Factor Is a Target Gene for Estrogen Receptor and Contributes to Breast Cancer Progression

  • Martine Perrot Applanat
  • Helene Buteau-Lozano
  • Marie Astrid Herve
  • Armelle Corpet
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Summary

Tumor growth requires the development and remodeling of the vascular system, involving paracrine signaling between various growth factors and endothelial receptors. Vascular endothelial growth factor (VEGF) is a key regulator of developmental, physiological and pathological neovascularization, especially involved in tumor growth. Recent studies indicate that 17β-estradiol (E2) modulates VEGF expression in breast cancer cells through transcriptional activation. We have investigated both the molecular mechanisms of E2-induction of VEGF expression and of VEGF control of breast cancer angiogenesis. In transient transfection assays using the VEGF promoter-luciferase construct, E2 increased VEGF transcriptional activity in MCF-7 cells and in MDA-MB-231 cotransfected with estrogen receptor (ERα or ERβ). The positive effect was abolished when MCF-7 cells were treated with the pure antiestrogen ICI 182,780 or the agonist/antagonist tamoxifen. We further identified an imperfect estrogen responsive element (ERE1520) in the VEGF promoter, which formed a complex with ERα or ERβ proteins in gel shift assay using MCF-7 or MDA-MB-231 nuclear extracts; the ERE sequence is involved in the transcriptionalregulation of VEGF in our experimental conditions. These results demonstrate that in breast cancer (BC) cells VEGF is a target gene for ERα or ERβ. To determine the role of VEGF in the progression of human breast carcinoma, we generated stable human breast carcinoma cells (MCF-7) overexpressing VEGF165 (V165 clones). Cells or control vector clones were implanted subcutaneously in athymic mice. Our in vivo findings show that overexpression of VEGF significantly decreased tumor uptake and increased tumor growth and angiogenesis in a murine model of BC.

Keywords

Breast Cancer Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor Expression Cell Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2008

Authors and Affiliations

  • Martine Perrot Applanat
    • 1
  • Helene Buteau-Lozano
  • Marie Astrid Herve
  • Armelle Corpet
  1. 1.Inserm Unit 553 Hospital Saint LouisParisFrance

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