Related Experiment Video
Updated: Mar 20, 2026

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
BET bromodomain-mediated interaction between ERG and BRD4 promotes prostate cancer cell invasion
Alexandra M Blee1,2, Shujun Liu3, Liguo Wang4
1Mayo Graduate School, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
Abstract:
Prostate cancer (PCa) that becomes resistant to hormone castration and next-generation androgen receptor (AR)-targeted therapies, called castration-resistant prostate cancer (CRPC), poses a significant clinical challenge. A better understanding of PCa progression and key molecular mechanisms could bring novel therapies to light. One potential therapeutic target is ERG, a transcription factor aberrantly up-regulated in PCa due to chromosomal rearrangements between androgen-regulated gene TMPRSS2 and ERG. Here we show that the most common PCa-associated truncated ERG T1-E4 (ERGΔ39), encoded by fusion between TMPRSS2 exon 1 and ERG exon 4, binds to bromodomain-1 (BD1) of bromodomain containing protein 4 (BRD4), a member of the bromodomain and extraterminal domain (BET) family. This interaction is partially abrogated by BET inhibitors JQ1 and iBET762. Meta-analysis of published ERG (T1-E4) and BRD4 chromatin immunoprecipitation-sequencing (ChIP-seq) data demonstrates overlap in a substantial portion of their binding sites. Gene expression profile analysis shows some ERG-BRD4 co-target genes are upregulated in CRPC compared to hormone-naïve counterparts. We provide further evidence that ERG-mediated invasion of PCa cells was significantly enhanced by an acetylation-mimicking mutation in ERG that augments the ERG-BRD4 interaction. Our findings reveal that PCa-associated ERG can interact and co-occupy with BRD4 in the genome, and suggest this druggable interaction is critical for ERG-mediated cell invasion and PCa progression.
Insights
Prostate cancer progression involves ERG and BRD4 interaction. Targeting this ERG-BRD4 binding offers a new therapeutic strategy for castration-resistant prostate cancer (CRPC).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Castration-resistant prostate cancer (CRPC) is a major clinical challenge.
- Understanding prostate cancer (PCa) progression mechanisms is crucial for novel therapies.
- ERG is a transcription factor often overexpressed in PCa due to gene fusions.
Purpose of the Study:
- To investigate the interaction between ERG and BRD4 in prostate cancer.
- To explore the functional significance of the ERG-BRD4 interaction in PCa progression.
Main Methods:
- Analyzing the binding of ERG T1-E4 to BRD4 BD1.
- Using BET inhibitors (JQ1, iBET762) to study the interaction.
- Performing meta-analysis of ChIP-seq data for ERG and BRD4.
- Analyzing gene expression profiles.
- Utilizing mutation analysis to assess ERG-BRD4 interaction effects.
Main Results:
- ERG T1-E4 directly binds to BRD4 BD1.
- BET inhibitors partially disrupt the ERG-BRD4 interaction.
- ERG and BRD4 share significant genomic binding sites.
- ERG-BRD4 co-target genes are upregulated in CRPC.
- An acetylation-mimicking mutation in ERG enhances ERG-BRD4 interaction and PCa cell invasion.
Conclusions:
- ERG interacts with and co-occupies genomic sites with BRD4 in PCa.
- The ERG-BRD4 interaction is critical for ERG-mediated cell invasion.
- This druggable interaction represents a potential therapeutic target for PCa progression.
Related Concept Videos
Cancer Cell Migration through Invadopodia
Mitogens and the Cell Cycle
Abnormal Proliferation
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
The Ras Gene
Ras is a...

