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Updated: Jan 19, 2026
16:24
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
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Distinct Roles for BET Family Members in Estrogen Receptor α Enhancer Function and Gene Regulation in Breast Cancer
Shino Murakami1,2,3, Rui Li1,2,3, Anusha Nagari1,2
1The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas.
Molecular Cancer Research : MCR
|September 26, 2019
Summary
Bromodomain and extraterminal (BET) proteins regulate estrogen receptor alpha (ERα) activity in breast cancer. BRD3 plays a unique role in controlling ERα enhancers, offering a potential therapeutic target for ER-positive breast cancers.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Bromodomain and extraterminal (BET) proteins are crucial coregulators of estrogen receptor alpha (ERα)-mediated transcription.
- BET inhibitors are investigated for solid tumors, including ER-positive breast cancers, but individual BET member roles are unclear.
Purpose of the Study:
- To investigate the roles of individual BET family members in estrogen (E2)-dependent gene expression in ERα-positive breast cancer cells.
- To explore the therapeutic potential of targeting BET proteins, specifically BRD3, in ER-positive breast cancers.
Main Methods:
- Chemical inhibition of BET proteins using JQ1.
- RNA interference (RNAi)-mediated depletion of BET family members (BRD2, BRD3, BRD4).
- Analysis of ERα-binding sites (ERBS) and gene expression.
Main Results:
- JQ1 inhibited E2-regulated gene expression and growth in breast cancer cells.
- Depletion of individual BET proteins showed partially redundant roles in ERα enhancer function and transcription.
- BRD3 demonstrated a unique role in sensing total BET protein levels and activity.
- BRD3 was recruited to specific ERα enhancers, including super enhancers, associated with highly E2-responsive genes.
Conclusions:
- BET family members play a critical and specific role in ERα-dependent gene transcription.
- BRD3's recruitment to and control of ERα enhancers present a therapeutic opportunity for ER-positive breast cancers using BET inhibitors.
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