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Updated: Jul 19, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Transgenic mouse model for rapid pharmacodynamic evaluation of antiandrogens
Katharine Ellwood-Yen1, John Wongvipat, Charles Sawyers
1Department of Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, California, USA.
Abstract:
Persistent androgen receptor signaling has been implicated as a critical factor in prostate cancer progression even at the hormone-refractory stage and provides strong rationale for developing novel androgen receptor antagonists. Traditional models for in vivo evaluation of antiandrogens are cumbersome because they rely on physiologic end points, such as the size of androgen-dependent tissues. Here, we describe a transgenic mouse (ARR2 Pb-Lux) that expresses luciferase specifically in the prostate in an androgen-dependent fashion. This signal is reduced by castration or by treatment with bicalutamide and can be quantified through noninvasive bioluminescent imaging. ARR2 Pb-Lux mice provide a novel method for rapid pharmacodynamic evaluation of novel pharmacologic compounds designed to inhibit androgen receptor signaling.
Insights
Researchers developed a new transgenic mouse model (ARR2 Pb-Lux) for prostate cancer research. This model allows for noninvasive tracking of androgen receptor signaling, aiding in the development of new anti-cancer drugs.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Persistent androgen receptor (AR) signaling drives prostate cancer progression, even in hormone-refractory disease.
- Developing novel AR antagonists is crucial for treating advanced prostate cancer.
- Current in vivo models for evaluating antiandrogens are limited by reliance on cumbersome physiological endpoints.
Purpose of the Study:
- To develop a novel transgenic mouse model for evaluating compounds targeting AR signaling.
- To establish a noninvasive method for quantifying AR signaling in vivo.
- To facilitate rapid pharmacodynamic assessment of novel antiandrogen therapies.
Main Methods:
- Generation of a transgenic mouse (ARR2 Pb-Lux) expressing luciferase in prostate tissue under AR-dependent regulation.
- Quantification of bioluminescent signal using noninvasive imaging.
- Evaluation of signal modulation following castration and antiandrogen (bicalutamide) treatment.
Main Results:
- The ARR2 Pb-Lux mouse model exhibits androgen-dependent luciferase expression specifically in the prostate.
- Bioluminescent signal intensity is significantly reduced by castration, confirming AR pathway dependency.
- Treatment with bicalutamide also effectively reduces the bioluminescent signal, validating the model's responsiveness.
Conclusions:
- The ARR2 Pb-Lux transgenic mouse is a valuable tool for noninvasive monitoring of AR signaling.
- This model enables rapid pharmacodynamic evaluation of novel agents targeting the AR pathway.
- It offers a significant improvement over traditional methods for assessing antiandrogen efficacy in vivo.
