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Updated: Jul 18, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Bisphenol A facilitates bypass of androgen ablation therapy in prostate cancer
Yelena B Wetherill1, Janet K Hess-Wilson, Clay E S Comstock
1Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, 3125 Eden Avenue, ML 0521, Cincinnati, OH 45267-0521, USA.
Abstract:
Prostatic adenocarcinomas depend on androgen for growth and survival. First line treatment of disseminated disease exploits this dependence by specifically targeting androgen receptor function. Clinical evidence has shown that androgen receptor is reactivated in recurrent tumors despite the continuance of androgen deprivation therapy. Several factors have been shown to restore androgen receptor activity under these conditions, including somatic mutation of the androgen receptor ligand-binding domain. We have shown previously that select tumor-derived mutants of the androgen receptor are receptive to activation by bisphenol A (BPA), an endocrine-disrupting compound that is leached from polycarbonate plastics and epoxy resins into the human food supply. Moreover, we have shown that BPA can promote cell cycle progression in cultured prostate cancer cells under conditions of androgen deprivation. Here, we challenged the effect of BPA on the therapeutic response in a xenograft model system of prostate cancer containing the endogenous BPA-responsive AR-T877A mutant protein. We show that after androgen deprivation, BPA enhanced both cellular proliferation rates and tumor growth. These effects were mediated, at least in part, through androgen receptor activity, as prostate-specific antigen levels rose with accelerated kinetics in BPA-exposed animals. Thus, at levels relevant to human exposure, BPA can modulate tumor cell growth and advance biochemical recurrence in tumors expressing the AR-T877A mutation.
Insights
Bisphenol A (BPA), an endocrine disruptor, can reactivate androgen receptor (AR) in prostate cancer cells. This study shows BPA promotes tumor growth and PSA levels in AR-T877A mutant prostate cancer models.
Area of Science:
- Oncology
- Endocrinology
- Environmental Health
Background:
- Prostate cancer growth is androgen-dependent, targeted by androgen deprivation therapy (ADT).
- Recurrent prostate cancers often show reactivated androgen receptor (AR) signaling despite ADT.
- Mutations in AR ligand-binding domain can restore AR activity, potentially influenced by environmental factors like BPA.
Purpose of the Study:
- To investigate the effect of Bisphenol A (BPA) on prostate cancer therapeutic response in a xenograft model with a BPA-responsive AR-T877A mutation.
- To determine if BPA exposure influences tumor growth and androgen receptor activity under conditions of androgen deprivation.
Main Methods:
- Utilized a xenograft model of prostate cancer harboring the endogenous AR-T877A mutant protein.
- Administered BPA to animals under androgen deprivation therapy.
- Monitored tumor proliferation rates, tumor growth, and prostate-specific antigen (PSA) levels.
Main Results:
- BPA exposure significantly enhanced cellular proliferation rates and tumor growth in the xenograft model.
- Prostate-specific antigen (PSA) levels increased with accelerated kinetics in BPA-exposed animals, indicating AR activity.
- These effects occurred at BPA levels relevant to human exposure.
Conclusions:
- Bisphenol A (BPA) can modulate tumor cell growth and accelerate biochemical recurrence in prostate cancers with the AR-T877A mutation.
- Environmental exposure to BPA may pose a risk for patients with specific forms of recurrent prostate cancer.
- Findings highlight the need to consider environmental endocrine disruptors in cancer therapy and recurrence.
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