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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

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Estrogen signaling and the DNA damage response in hormone dependent breast cancers

C Elizabeth Caldon1

  • 1Genome and Replication Stability Group, The Kinghorn Cancer Centre, Garvan Institute of Medical Research , Sydney, NSW , Australia ; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia , Sydney, NSW , Australia.

Frontiers in Oncology
|May 27, 2014
PubMed

Insights

Estrogen promotes breast cancer by disrupting DNA repair mechanisms. This signaling pathway suppresses DNA damage response and apoptosis, favoring cancer cell proliferation and impacting treatment efficacy.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cancer Research

Background:

  • Estrogen is crucial for breast tissue development but high levels increase breast cancer risk.
  • Estrogen's role in breast cancer may involve inducing DNA damage.
  • Understanding estrogen's impact on DNA damage response is vital for hormone-dependent cancers.

Purpose of the Study:

  • To discuss mechanisms by which estrogen alters DNA damage response (DDR) and repair.
  • To investigate estrogen receptor signaling's feedback on DDR proteins.
  • To hypothesize how estrogen signaling favors proliferation over repair and apoptosis.

Main Methods:

  • Review of mechanisms linking estrogen to DNA damage.
  • Analysis of estrogen's regulation of key DDR proteins (ATM, ATR, CHK1, BRCA1, p53).
  • Examination of feedback loops between DDR proteins and estrogen receptor signaling.

Main Results:

  • Estrogen signaling converges to suppress effective DNA repair and apoptosis.
  • This suppression favors cancer cell proliferation.
  • Altered DDR/DNA repair proteins in estrogen-responsive breast cancer further modify DNA damage processing.

Conclusions:

  • Estrogen signaling suppresses DNA damage response and apoptosis, promoting proliferation in breast cancer.
  • This mechanism impacts the processing of estrogen-induced DNA damage and other genotoxic insults.
  • Estrogen's modulation of DDR affects therapeutic responses to anti-hormone therapy and chemotherapy.
Keywords:
BRCA1DDRDNA damage responseDNA repairbreast cancerestrogen receptorp53tamoxifen

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