The co regulators SRC 1 and SMRT are involved in interleukin 6 induced androgen receptor activation
BackgroundThe 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.MethodsThe 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.ResultsIL 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 theAR SMRT interaction and a marked reduction was detected at 50 ng/mL (P<0.05).ConclusionsIL 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 inducedARactivation 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.
European Cytokine Network