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Human Prostate Diagram

Investigating Bisphenol A (BPA) Exposure in Prostate Cancer Risk

Prostate Cancer and Prostate Stem Cells

Prostate cancer affects approximately 1 in 9 men. In the United States this year, about 191,930 cases of prostate cancer will be diagnosed and approximately 33,330 deaths will occur due to prostate cancer (second to lung cancer). Although not perfect, screening for prostate cancer can be performed using the prostate-specific antigen, or PSA, test, which measures PSA levels in the blood. If PSA levels are higher than normal, a biopsy and further investigation may be warranted.

Prostate stem cells contribute to long-term maintenance of the prostate epithelium, and although the identity of the prostate stem cell is debated, new culturing techniques have allowed for a more detailed investigation into prostate stem cells. In particular, Lifeline® normal human prostate epithelial cells have previously (opens in new window) been shown to form spheroid-like structures in culture (termed prostaspheres). These prostaspheres contain prostate stem cells and BrdU labeling studies have demonstrated that prostate stem cell dynamics can be evaluated using this system.

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Lifeline Prostate Epithelial Cells in Prostate Cancer Research

Bisphenol A (BPA)—a widespread chemical—has been under investigation for its potential role in increasing cancer risk. In a 2018 study, Prins and colleagues (opens in new window) set out to determine the effects of BPA on the prostate epithelium. They first examined prostate histopathology in a set of Sprague-Dawley rats treated with: vehicle, ethinyl estradiol (EE; a synthetic form of estrogen), continuous BPA (BPA from Day 6 of gestation through 1 year of age), stop-dose BPA (BPA from Day 6 of gestation through postnatal Day 21), or stop-dose BPA plus testosterone + estradiol (T+E; used to promote cancer development and assess the effects of BPA in a cancer-prone model). They found that BPA treatment alone did not significantly alter prostate histology. However, rats that were exposed to various stop-doses of BPA (2.5, 25, or 250 μg/kg) plus T+E displayed increased severity of prostatic intraepithelial neoplasia (a precancerous lesion), and rats in the 2.5 μg/kg BPA plus T+E group had higher rates of ductal adenocarcinoma (a malignant lesion).

Next, the authors examined whether BPA exposure affected stem and progenitor cell number and differentiation capacity in the dorso-lateral prostate of rats treated daily for 6 months with vehicle, EE, or BPA (2.5, 25, or 250 μg/kg). By analyzing prostate spheroids from these treatment groups in culture, the authors were able to show that the number of stem cells (assessed by prostate spheroid number) increased in rats treated with EE or 2.5 μg/kg BPA. Additionally, in rats treated with 25 or 250 μg/kg BPA, prostate spheres were larger, indicating increased proliferation of progenitor cells. The prostate epithelium contains two major differentiated cell types: basal and luminal cells. In particular, gene expression analysis of these rat prostate-derived spheroids showed that BPA-induced morphological changes were accompanied by increased expression of basal progenitor markers and decreased expression of luminal progenitor markers.

Using Lifeline normal human prostate epithelial cells, the authors next capitalized on their previously developed human prostasphere-based BrdU label retention assay to assess stem and progenitor cell dynamics (described in a previous blog post here). Their analysis showed that human prostaspheres exposed to 2.5 mM BPA for 7 days had significantly greater numbers of longer-term BrdU-labeled cells compared with those treated with vehicle or 25 nM BPA.

Together, the results of this study illustrate that low doses of BPA disrupt prostate stem and progenitor cell dynamics and homeostasis.

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Prostate cancer statistics from www.cancer.org (opens in new window).

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