Transgenic Mouse Model for Rapid Pharmacodynamic Evaluation of Antiandrogens
Open Access
- 1 November 2006
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 66 (21) , 10513-10516
- https://doi.org/10.1158/0008-5472.can-06-1397
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. (Cancer Res 2006; 66(21): 10513-6)Keywords
This publication has 11 references indexed in Scilit:
- EZC-Prostate Models Offer High Sensitivity and Specificity for Noninvasive Imaging of Prostate Cancer Progression and Androgen Receptor ActionCancer Research, 2006
- A luciferase transgenic mouse model: visualization of prostate development and its androgen responsiveness in live animalsJournal of Molecular Endocrinology, 2005
- Regulation of androgen receptor levels: Implications for prostate cancer progression and therapyJournal of Cellular Biochemistry, 2005
- HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stabilityCancer Cell, 2004
- Bicalutamide (Casodex®) in the treatment of prostate cancerExpert Review of Anticancer Therapy, 2004
- Molecular determinants of resistance to antiandrogen therapyNature Medicine, 2003
- Myc-driven murine prostate cancer shares molecular features with human prostate tumorsCancer Cell, 2003
- The development of androgen-independent prostate cancerNature Reviews Cancer, 2001
- A Small Composite Probasin Promoter Confers High Levels of Prostate-Specific Gene Expression through Regulation by Androgens and Glucocorticoids in Vitro and in Vivo**This work was supported by R01-DK-55748 from the NIH and the Frances Williams Preston Laboratories of the T. J. Martell Foundation. Transgenic mice were bred by the Transgenic Core/ES Cell Shared Resource of the Vanderbilt-Ingram Cancer Center (NCI Grant 2P30-CA-68485–05).Endocrinology, 2000
- Combined treatment of Dunning R3327 rat prostatic tumor with the 5α-reductase inhibitor PNU 157706 and the antiandrogen bicalutamideCancer Chemotherapy and Pharmacology, 2000