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Estrogen Signaling in ERα-Negative Breast Cancer: ERβ and GPER

Rainer Girgert1, Günter Emons1, Carsten Gründker1

  • 1Department of Gynecology and Obstetrics, University Medicine Göttingen, Göttingen, Germany.

Frontiers in Endocrinology
|January 29, 2019
PubMed

Insights

Estrogen receptor signaling in ERα-negative breast tumors is explored. This review details the roles of ERβ and GPER in non-genomic pathways, offering insights into potential therapeutic targets for difficult-to-treat breast cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Estrogen receptors (ERα, ERβ, GPER) regulate breast tumor growth.
  • Anti-estrogen therapy effectiveness relies on ERα presence.
  • ERα-negative breast cancers, including triple-negative, lack ERα and require alternative treatment strategies.

Purpose of the Study:

  • To review the signaling pathways of ERβ and GPER in ERα-negative breast tumors.
  • To highlight recent findings on GPER-mediated non-genomic effects.
  • To explore potential therapeutic targets beyond ERα.

Main Methods:

  • Literature review of signaling pathways involving ERβ and GPER.
  • Analysis of non-genomic signaling mechanisms.
  • Summary of GPER-dependent activation of FOXO3a, Hippo-pathway, and HOTAIR.

Main Results:

  • ERβ and GPER play significant roles in ERα-negative breast tumor signaling.
  • GPER mediates non-genomic effects, including EGF-receptor transactivation.
  • Emerging evidence shows GPER activates FOXO3a, Hippo-pathway, and HOTAIR.

Conclusions:

  • ERβ and GPER represent crucial targets for ERα-negative breast cancer treatment.
  • Understanding these pathways can lead to novel therapeutic interventions.
  • Further research into GPER-mediated signaling is warranted for clinical application.
Keywords:
ERαERα-negative breast cancerERβGPERestrogen signaling

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