Hypoxia and estrogen receptor profile influence the responsiveness of human breast cancer cells to estradiol and antiestrogens

D. Coradini, C. Pellizzaro, A. Speranza, M. G. Daidone

Research output: Contribution to journalArticle

Abstract

Angiogenesis activation mediated by vascular endothelial growth factor (VEGF) is one of the factors that can cause antiestrogen treatment failure in estrogen receptor (ER)-positive breast cancer patients. Since VEGF synthesis is modulated not only by hypoxia but also by steroid hormones, we investigated the relationship between hypoxic and estrogenic/antiestrogenic stimuli in two human breast cancer cell lines expressing both ERα and ERβ (MCF7) or only ERβ (MDA-MB231). In both cell lines, the VEGF level was significantly influenced by hypoxic conditions and in antiestrogen-responsive MCF7 cells, this effect was not counteracted by tamoxifen or ICI 182,780, thus providing an experimental explanation for the resistance to endocrine treatment observed in patients with ER-positive tumors. In MDA-MB231 cells, estradiol significantly reduced the VEGF level, suggesting that through the ERβ isoform it may function as a negative modulator of VEGF synthesis under hypoxia, and providing evidence for a complex interplay of the estrogen-dependent and hypoxia-dependent pathways.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalCellular and Molecular Life Sciences
Volume61
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • Breast cancer cell line
  • Estradiol
  • HIF-1α
  • Tamoxifen
  • VEGF

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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