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Updated: Jun 19, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Published on: January 12, 2020

Notch-1 activates estrogen receptor-alpha-dependent transcription via IKKalpha in breast cancer cells

L Hao1, P Rizzo, C Osipo

  • 1Breast Cancer Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, USA.

Oncogene
|October 20, 2009
PubMed

Insights

Notch-1 signaling promotes estrogen receptor-alpha (ERalpha)-positive breast cancer growth by increasing ERalpha-responsive gene transcription. This occurs through a novel chromatin crosstalk mechanism involving Notch-1 and ERalpha, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Estrogen receptor-alpha (ERalpha)-positive breast cancers (approx. 80%) are treated with anti-estrogens, but resistance is a major challenge.
  • Estrogen inhibits Notch signaling, while anti-estrogens or estrogen withdrawal activate it.
  • Combined inhibition of Notch and estrogen signaling shows synergistic effects in ERalpha-positive breast cancer models.

Purpose of the Study:

  • To elucidate the mechanisms by which Notch-1 promotes the growth of ERalpha-positive breast cancer cells.
  • To investigate the role of Notch-1 in regulating ERalpha-responsive gene transcription.

Main Methods:

  • Demonstrated Notch-1's effect on ERalpha-responsive gene transcription in breast cancer models.
  • Investigated a novel chromatin crosstalk mechanism involving Notch-1 and ERalpha.
  • Utilized chromatin immunoprecipitation and gene expression analysis to study protein-DNA interactions and transcriptional regulation.

Main Results:

  • Notch-1 increases the transcription of ERalpha-responsive genes, irrespective of estrogen presence.
  • A novel chromatin crosstalk mechanism was identified, involving IKKalpha-dependent recruitment of Notch-CSL-MAML1 transcriptional complexes (NTC) and ERalpha.
  • This interaction promotes p300 recruitment, enhancing transcriptional activity of ERalpha-target genes.

Conclusions:

  • A previously unknown Notch-1/ERalpha chromatin crosstalk mechanism mediates Notch signaling in ERalpha-positive breast cancer.
  • This crosstalk regulates the transcriptional functions of ERalpha, contributing to breast cancer cell growth.
  • Targeting this Notch-1/ERalpha interaction may offer new therapeutic strategies for endocrine-resistant breast cancer.

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