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Evidence for the notch signaling pathway on the role of estrogen in angiogenesis

R Soares1, G Balogh, S Guo

  • 1Institute of Molecular Pathology and Immunology of the University of Porto, 4200 Porto, Portugal. raquel.soares@ipatimup.pt

Molecular Endocrinology (Baltimore, Md.)
|June 12, 2004
PubMed

Insights

17 beta-estradiol stimulates angiogenesis in breast cancer by activating Notch signaling. This pathway involves increased Jagged1 and Notch1 expression, crucial for tumor microvessel formation and growth.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Estrogen plays a role in breast cancer progression.
  • Angiogenesis is critical for tumor growth and metastasis.
  • The Notch signaling pathway is involved in cell differentiation and development.

Purpose of the Study:

  • To investigate the molecular mechanisms linking 17 beta-estradiol to angiogenesis.
  • To determine the role of Notch signaling in 17 beta-estradiol-induced angiogenesis.
  • To explore the potential of targeting Notch signaling in breast cancer therapy.

Main Methods:

  • cDNA arrays to measure gene expression in MCF7 cells.
  • Estrogen antagonist (ICI182,780) treatment.
  • Notch1 reporter gene assays and co-culture assays.
  • In vivo studies using 17 beta-estradiol-treated nude mice.
  • Endothelial cell culture and Matrigel assays.
  • Analysis of hypoxia-inducible factor 1 alpha (HIF-1α) expression.

Main Results:

  • 17 beta-estradiol significantly increased Jagged1 and Notch1 expression in MCF7 cells.
  • Estrogen antagonist abrogated Jagged1 expression.
  • Notch1 and Jagged1 expression were upregulated in endothelial cells and possessed estrogen-responsive elements.
  • 17 beta-estradiol activated Notch signaling in breast cancer cells.
  • In vivo, 17 beta-estradiol treatment increased Notch1 expression and tumor microvessel density.
  • Notch1 signaling is essential for endothelial cell tube formation.
  • Notch1 expression correlated with increased HIF-1α, a key angiogenic factor.

Conclusions:

  • Notch signaling is implicated in the cross-talk between 17 beta-estradiol and angiogenesis.
  • 17 beta-estradiol promotes angiogenesis in breast cancer via the Notch pathway.
  • Targeting Notch signaling may offer a therapeutic strategy for estrogen-dependent breast cancers.

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