Ellwood-Yen Katharine, Wongvipat John, Sawyers Charles
Department of Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, California, USA.
Cancer Res. 2006 Nov 1;66(21):10513-6. doi: 10.1158/0008-5472.CAN-06-1397.
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.
持续的雄激素受体信号传导被认为是前列腺癌进展的关键因素，即使在激素难治性阶段也是如此，这为开发新型雄激素受体拮抗剂提供了有力的理论依据。用于体内抗雄激素评估的传统模型很繁琐，因为它们依赖于生理终点，例如雄激素依赖性组织的大小。在此，我们描述了一种转基因小鼠（ARR2 Pb-Lux），其以雄激素依赖性方式在前列腺中特异性表达荧光素酶。这种信号可通过去势或比卡鲁胺治疗而降低，并且可以通过非侵入性生物发光成像进行量化。ARR2 Pb-Lux小鼠为快速药效学评估旨在抑制雄激素受体信号传导的新型药理化合物提供了一种新方法。
