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Cooperation between Polycomb and androgen receptor during oncogenic transformation
Jonathan C Zhao1, Jianjun Yu, Christine Runkle
1Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Genome Research
|December 20, 2011
Summary
Androgen receptor (AR) acts as a transcriptional repressor, not just an activator. This unexpected role in gene silencing contributes to stem cell-like states and prostate cancer progression.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The androgen receptor (AR) is a key transcription factor in prostate biology.
- Its role as a transcriptional activator is well-established, but downstream pathways remain unclear.
Purpose of the Study:
- To investigate the global function of the androgen receptor (AR) in gene regulation.
- To elucidate the mechanisms and implications of AR-mediated gene repression.
Main Methods:
- Integrative analysis of genome-wide AR occupancy and gene expression data.
- Chromatin immunoprecipitation and gene expression profiling were employed.
Main Results:
- AR functions as a global transcriptional repressor, mediated by androgen-responsive elements (ARE).
- AR repression involves EZH2 and repressive chromatin remodeling.
- AR-repressed genes in stem cells exhibit bivalent histone modifications (H3K4me3/H3K27me3), maintaining pluripotency.
- Silencing of these genes is observed in castration-resistant prostate cancer, correlating with dedifferentiation and tumor progression.
Conclusions:
- AR unexpectedly acts as a transcriptional repressor, inhibiting non-prostatic differentiation.
- Excessive AR signaling drives cancerous dedifferentiation and tumor progression by silencing differentiation regulators.
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