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NFκB affects estrogen receptor expression and activity in breast cancer through multiple mechanisms

Jonna Frasor1, Lamiaa El-Shennawy2, Joshua D Stender3

  • 1Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.

Molecular and Cellular Endocrinology
|December 3, 2014
PubMed

Insights

Nuclear factor-kappa B (NFκB) signaling impacts estrogen receptor (ER) activity in breast cancer. This interaction affects treatment response and tumor outcomes, highlighting a critical area for therapeutic development.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Estrogen receptor (ER) and Nuclear Factor-kappa B (NFκB) are key transcription factors with known interactions.
  • ER's repression of NFκB is linked to estrogen's anti-inflammatory effects.
  • The influence of NFκB signaling on ER activity is less understood but critical in ER-positive breast cancer.

Purpose of the Study:

  • To review the mechanisms by which NFκB signaling affects ER activity.
  • To highlight the clinical relevance of NFκB-ER interactions in breast cancer treatment resistance.

Main Methods:

  • Literature review of studies investigating NFκB and ER interactions.
  • Analysis of molecular mechanisms governing NFκB's influence on ER.

Main Results:

  • NFκB signaling can down-regulate ER expression.
  • NFκB enhances ER recruitment to DNA, increasing transcriptional activity.
  • NFκB can potentiate ER-dependent gene repression.
  • These interactions are observed for both liganded and unliganded ER.

Conclusions:

  • NFκB signaling significantly modulates ER activity through multiple mechanisms.
  • These modulations can lead to resistance to endocrine therapies in ER-positive breast cancer.
  • Understanding NFκB-ER crosstalk is crucial for improving outcomes in breast cancer patients.
Keywords:
Breast cancerEstrogen receptorNFκBTamoxifen

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