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Updated: Jul 10, 2026
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Unique bisphenol A transcriptome in prostate cancer: novel effects on ERbeta expression that correspond to androgen
Janet K Hess-Wilson1, Siobhan L Webb, Hannah K Daly
1Department of Cell and Cancer Biology, University of Cincinnati College of Medicine, Ohio 45267-0521, USA.
Background:
Prostatic adenocarcinomas are dependent on androgen receptor (AR) activity for growth and progression, and therapy for disseminated disease depends on ablation of AR activity. Recurrent tumors ultimately arise wherein AR has been re-activated. One mechanism of AR restoration is via somatic mutation, wherein cells containing mutant receptors become susceptible to activation by alternative ligands, including bisphenol A (BPA). In tumors with specific AR mutations, BPA promotes therapeutic bypass, suggesting significant negative impact to the clinical management of prostate cancer.
Objective:
Our goal was to determine the mechanism of BPA action in cancer cells carrying BPA-responsive AR mutants.
Methods:
The molecular signature of BPA activity in prostate cancer cells harboring mutant AR was delineated via genetic microarray analysis. Specificity of BPA action was assessed by comparison with the molecular signature elicited by dihydrotestosterone (DHT).
Results:
BPA and DHT elicited distinct transcriptional signatures in prostate cancer cells expressing the BPA-responsive mutant AR-T877A. BPA dramatically attenuated estrogen receptor beta (ERbeta) expression; this finding was specific to prostate tumor cells in which BPA induces cellular proliferation.
Conclusions:
BPA induces a distinct gene expression signature in prostate cancer cells expressing somatic AR mutation, and a major molecular consequence of BPA action is down-regulation of ERbeta. Since ERbeta functions to antagonize AR function and AR-dependent proliferation, these findings reveal a novel mechanism by which BPA likely regulates cellular proliferation. Future investigation directed at dissecting the importance of ERbeta in the proliferative response to BPA will establish the contribution of this event to adverse effects associated with human exposure.
Insights
Bisphenol A (BPA) activates prostate cancer cells with mutated androgen receptors (AR) by down-regulating estrogen receptor beta (ERbeta), a key AR antagonist. This mechanism promotes tumor growth and therapeutic resistance in prostate cancer.
Area of Science:
- Endocrinology
- Molecular Oncology
- Prostate Cancer Research
Background:
- Prostate cancer growth is driven by androgen receptor (AR) activity.
- Therapies aim to inhibit AR, but recurrent tumors often reactivate AR.
- Somatic mutations can lead to AR reactivation, making cancer cells responsive to alternative ligands like bisphenol A (BPA).
Purpose of the Study:
- To elucidate the mechanism by which BPA affects prostate cancer cells harboring BPA-responsive AR mutations.
- To understand how BPA influences gene expression in the context of AR mutations.
Main Methods:
- Genetic microarray analysis was employed to determine the molecular signature of BPA activity in prostate cancer cells with mutant AR.
- The effects of BPA were compared to those of dihydrotestosterone (DHT) to assess specificity.
Main Results:
- BPA and DHT induced distinct transcriptional profiles in prostate cancer cells with the AR-T877A mutation.
- BPA significantly reduced estrogen receptor beta (ERbeta) expression, specifically in prostate tumor cells where it stimulated proliferation.
Conclusions:
- BPA triggers a unique gene expression pattern in prostate cancer cells with AR mutations.
- A critical effect of BPA is the downregulation of ERbeta, which normally opposes AR function.
- This suggests a novel pathway where BPA-induced ERbeta reduction contributes to AR-dependent cellular proliferation and potential therapeutic bypass.
