Truica C I, Byers S, Gelmann E P
Lombardi Cancer Center, Georgetown University, Washington, DC 20007-2197, USA.
Cancer Res. 2000 Sep 1;60(17):4709-13.
beta-Catenin is a multifunctional molecule with important roles in intercellular adhesion and signal transduction. We reported previously that beta-catenin is mutated in human prostate cancer. In this study, we investigated the role of beta-catenin mutations on androgen receptor (AR) signaling. beta-Catenin significantly enhanced androgen-stimulated transcriptional activation by the AR. beta-Catenin also increased AR transcriptional activation by androstenedione and estradiol and diminished the antagonism of bicalutamide. Coimmunoprecipitation of beta-catenin with AR from LNCaP prostate cancer cells showed that the two molecules are present in the same complex. The amount of beta-catenin in complex with AR was increased by androgen. These findings implicate beta-catenin in the regulation of AR function and support a role for beta-catenin mutations in the pathogenesis of prostate cancer.
β-连环蛋白是一种多功能分子，在细胞间黏附和信号转导中发挥重要作用。我们之前报道过β-连环蛋白在人类前列腺癌中发生突变。在本研究中，我们调查了β-连环蛋白突变对雄激素受体（AR）信号传导的作用。β-连环蛋白显著增强了AR介导的雄激素刺激的转录激活。β-连环蛋白还增加了雄烯二酮和雌二醇对AR的转录激活作用，并减弱了比卡鲁胺的拮抗作用。从LNCaP前列腺癌细胞中对β-连环蛋白与AR进行免疫共沉淀显示，这两种分子存在于同一复合物中。雄激素增加了与AR结合的β-连环蛋白的量。这些发现表明β-连环蛋白参与AR功能的调节，并支持β-连环蛋白突变在前列腺癌发病机制中的作用。
