TY - EJOU AU - Wang, Qi AU - Wang, Hui AU - Ju, Qiang AU - Ding, Zhen AU - Ge, Xing AU - Shi, Qiao-Mei AU - Zhou, Ji-Long AU - Zhou, Xiao-Long AU - Zhang, Jin-Peng AU - Zhang, Mei-Rong AU - Yu, Hong-Min AU - Xu, Li-Chun TI - The co-regulators SRC-1 and SMRT are involved in interleukin-6-induced androgen receptor activation T2 - European Cytokine Network PY - 2016 VL - 27 IS - 4 SN - 1952-4005 AB - Background: The androgen receptor (AR) can be stimulated by interleukin-6 (IL-6) in the absence of androgens to induce prostate cancer progression. The purpose of this study was to investigate whether the co-activator steroid receptor coactivator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) are involved in IL-6-induced AR activation. Methods: The effects of IL-6 on LNCaP cell proliferation were monitored using real-time cell analysis (RTCA) iCELLigence system. The impacts of IL-6 on the association of the AR with SRC-1 and SMRT were investigated using the mammalian two-hybrid assay. Results: IL-6 increased the proliferation of LNCaP cells with maximal induction at 50 ng/mL. The AR-SRC-1interaction was enhanced by IL-6, with maximal induction at the concentration of 50 ng/mL (P<0.05). IL-6 decreased the AR-SMRT interaction and a marked reduction was detected at 50 ng/mL (P<0.05). Conclusions: IL-6 enhances LNCaP cells proliferation, which suggests that IL-6 might cause AR-positive prostate cancer growth through activation of the AR. The mechanism of IL-6-induced AR activation is mediated through enhancing AR-SRC-1 interaction and inhibiting AR-SMRT interaction. We have shown a significant role for SRC-1 and SMRT in modulating IL-6-induced AR transactivation. KW - steroid receptor coactivator-1 KW - silencing mediator for retinoid and thyroid hormone receptors KW - androgen receptor KW - interleukin-6 DO - 10.1684/ecn.2016.0380