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Updated: Jul 4, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium
M Stanbrough1, I Leav, P W Kwan
1Cancer Biology Program, Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Abstract:
Prostate cancer (PCa) is an androgen dependent disease that can be treated by androgen ablation therapy, and clinical trials are under way to prevent PCa through the reduction of androgen receptor (AR) activity. However, there are no animal models of AR-mediated prostatic neoplasia, and it remains unclear whether the AR is a positive or negative regulator of cell growth in normal prostate secretory epithelium. To assess the direct effects of the AR in prostate epithelium, a murine AR transgene regulated by the rat probasin promoter (Pb) was used to generate transgenic mice expressing increased levels of AR protein in prostate secretory epithelium. The prostates in younger (<1 year) Pb-mAR transgenic mice were histologically normal, but Ki-67 immunostaining revealed marked increases in epithelial proliferation in ventral prostate and dorsolateral prostate. Older (>1 year) transgenic mice developed focal areas of intraepithelial neoplasia strongly resembling human high-grade prostatic intraepithelial neoplasia (PIN), a precursor to PCa. These results demonstrate that the AR is a positive regulator of cell growth in normal prostate epithelium and provide a model system of AR-stimulated PIN that can be used for assessing preventative hormonal therapies and for identifying secondary transforming events relevant to human PCa.
Insights
The androgen receptor (AR) promotes prostate cell growth and can lead to prostatic intraepithelial neoplasia (PIN), a precursor to prostate cancer (PCa). This study develops a new mouse model for AR-driven PIN, aiding research into PCa prevention.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Prostate cancer (PCa) is androgen-dependent, with androgen ablation therapy being a primary treatment.
- The role of the androgen receptor (AR) in regulating prostate epithelial cell growth is not fully understood.
- Existing animal models do not fully recapitulate AR-mediated prostatic neoplasia.
Purpose of the Study:
- To investigate the direct role of the AR in prostate epithelium.
- To develop a novel animal model for studying AR-mediated prostatic intraepithelial neoplasia (PIN).
- To assess the AR as a potential target for PCa prevention strategies.
Main Methods:
- Generation of transgenic mice with increased AR expression in prostate secretory epithelium using the rat probasin promoter (Pb-mAR).
- Histological analysis and Ki-67 immunostaining to evaluate epithelial proliferation and neoplasia.
- Comparison of younger and older transgenic mice to observe disease progression.
Main Results:
- Pb-mAR transgenic mice showed increased epithelial proliferation in the ventral and dorsolateral prostate.
- Older transgenic mice (>1 year) developed focal intraepithelial neoplasia resembling human high-grade PIN.
- The AR was confirmed as a positive regulator of cell growth in normal prostate epithelium.
Conclusions:
- The androgen receptor (AR) is a positive regulator of cell growth in prostate epithelium.
- The developed Pb-mAR transgenic mouse model mimics AR-stimulated PIN, a precursor to PCa.
- This model is valuable for evaluating preventative hormonal therapies and identifying secondary events in PCa development.
