Estrogen Receptor Beta Pharmacology in the Prostate

描述（申请人提供）：最近，ERbeta被证明可以抑制前列腺中的雄激素受体信号传导，因此可能在前列腺生长和分化的调节中发挥关键作用。本研究的目的是阐明ERbeta在雄激素反应性前列腺细胞模型中的作用。为此，erβ相互作用蛋白将使用T7噬菌体展示系统进行鉴定。在验证了这些蛋白-蛋白相互作用之后，我们建议确定这些蛋白在雄激素介导的前列腺生长机制中调节ERbeta的生理和药理作用中的作用。为此，我们提出以下具体目标：雄激素反应性前列腺模型细胞系中与erβ配体复合物相互作用的因子鉴定。目标2。哺乳动物细胞中erβ相互作用蛋白的验证和表征。目标3。雄激素反应性前列腺细胞系中erβ -辅助因子募集差异的生物学后果评估。

DESCRIPTION (provided by applicant): Recently, ERbeta was demonstrated to inhibit androgen receptor signaling in the prostate and thus is likely to play a pivotal role in the regulation of prostate growth and differentiation. The objective of this proposal is to elucidate the role of ERbeta in androgen-responsive prostate cell models. To do this, ERbeta-interacting proteins will be identified using a T7 phage display system. Following the validation of these protein-protein interactions, we propose to determine the role of these proteins in modulating the physiological and pharmacological actions of ERbeta in androgen-mediated prostate growth mechanisms. To accomplish this, we propose the following specific aims: Aim 1. Identification of factors that interact with ERbeta-ligand complexes in androgen-responsive prostate model cell lines. Aim 2. Validation and characterization of ERbeta-interacting proteins in mammalian cells. Aim 3. Evaluation of the biological consequences of differential ERbeta-cofactor recruitment in androgen-responsive prostate cell lines.