Junicho A, Matsuda T, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A
Department of Urology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Biochem Biophys Res Commun. 2000 Nov 11;278(1):9-13. doi: 10.1006/bbrc.2000.3753.
Protein inhibitor of activated STAT3 (PIAS3) is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3). PIAS3 binds to STAT3 and inhibits its DNA-binding activity, and thereby STAT3-mediated gene activation. PIAS1, another member of the PIAS family, was recently shown to interact with the androgen receptor (AR), a nuclear hormone receptor that has an important role in both physiological and pathological processes, and acts as a cofactor for AR. Here we demonstrate that PIAS3 is expressed in prostate cancer cells and its expression is induced in response to dihydrotestosterone (DHT) treatment. Ectopic overexpression of PIAS3 suppressed AR-mediated gene activation induced by DHT-stimulation in LNCaP cells. We provide evidence that these activities were due to direct physical interactions between PIAS3 and AR. These results indicate that PIAS3 acts as a coregulator of AR signaling pathway in prostate cancer cells.
活化STAT3的蛋白抑制剂（PIAS3）是信号转导子和转录激活子3（STAT3）的特异性抑制剂。PIAS3与STAT3结合并抑制其DNA结合活性，从而抑制STAT3介导的基因激活。PIAS家族的另一个成员PIAS1最近被证明与雄激素受体（AR）相互作用，AR是一种核激素受体，在生理和病理过程中都起着重要作用，并作为AR的辅因子。在这里，我们证明PIAS3在前列腺癌细胞中表达，并且其表达在二氢睾酮（DHT）处理后被诱导。PIAS3的异位过表达抑制了LNCaP细胞中DHT刺激诱导的AR介导的基因激活。我们提供的证据表明，这些活性是由于PIAS3与AR之间的直接物理相互作用。这些结果表明，PIAS3在前列腺癌细胞中作为AR信号通路的共调节因子发挥作用。
