The co-regulators SRC-1 and SMRT are involved in interleukin-6-induced androgen receptor activation.

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. 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. 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). 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.

Citation

Qi Wang, Hui Wang, Qiang Ju, Zhen Ding, Xing Ge, Qiao-Mei Shi, Ji-Long Zhou, Xiao-Long Zhou, Jin-Peng Zhang, Mei-Rong Zhang, Hong-Min Yu, Li-Chun Xu. The co-regulators SRC-1 and SMRT are involved in interleukin-6-induced androgen receptor activation. European cytokine network. 2016 Nov 01;27(4):108-113

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PMID: 28396297

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