Matsuda T, Junicho A, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A
Department of Immunology, Department of Urology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194, Japan.
Biochem Biophys Res Commun. 2001 Apr 27;283(1):179-87. doi: 10.1006/bbrc.2001.4758.
Interleukin 6 (IL-6) plays important roles in the immune system, hematopoiesis, as well as the growth of various tumors. Androgens are important in the initiation and progression of prostate cancer and their effects are mediated by androgen receptor (AR). Here we present a molecular mechanism for the effects of IL-6 on prostate cancer cells through a cross-talk between IL-6 and AR signaling pathways. IL-6-induced activation of signal transducer and activator of transcription 3 (STAT3) was augmented by AR in the presence of dihydrotestosterone (DHT). In addition, DHT treatment augmented endogenous STAT3-mediated gene expression by IL-6. Conversely, DHT-induced AR activity was increased by IL-6, and a dominant negative form of STAT3 inhibited AR activation. In contrast, DHT-mediated enhancement of STAT3 activation was inhibited by flutamide, an AR antagonist. We provide evidence that these activities are due to direct physical interactions between STAT3 and AR in prostate cancer cells.
白细胞介素6（IL-6）在免疫系统、造血作用以及各种肿瘤的生长过程中发挥着重要作用。雄激素在前列腺癌的发生和发展过程中起着重要作用，其作用是由雄激素受体（AR）介导的。在此，我们通过白细胞介素6（IL-6）与雄激素受体（AR）信号通路之间的相互作用，阐述了IL-6对前列腺癌细胞作用的分子机制。在双氢睾酮（DHT）存在的情况下，AR增强了IL-6诱导的信号转导和转录激活因子3（STAT3）的激活。此外，DHT处理增强了IL-6诱导的内源性STAT3介导的基因表达。相反，IL-6增加了DHT诱导的AR活性，而STAT3的显性阴性形式抑制了AR的激活。相比之下，AR拮抗剂氟他胺抑制了DHT介导的STAT3激活增强。我们提供的证据表明，这些活性是由于前列腺癌细胞中STAT3与AR之间直接的物理相互作用所致。
