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 theAR-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-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.

中文翻译：

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协同调节剂SRC-1和SMRT参与白介素6诱导的雄激素受体激活。

背景

在不存在雄激素的情况下，白细胞介素6（IL-6）可以刺激雄激素受体（AR）诱导前列腺癌的进展。这项研究的目的是调查类视色素和甲状腺激素受体（SMRT）的共激活激素受体coactivator-1（SRC-1）和共抑制沉默沉默介体是否参与IL-6诱导的AR激活。

方法

使用实时细胞分析（RTCA）iCELLigence系统监测IL-6对LNCaP细胞增殖的影响。使用哺乳动物两杂交试验研究了IL-6对AR与SRC-1和SMRT缔合的影响。

结果

IL-6以50 ng / mL的最大诱导量增加LNCaP细胞的增殖。IL-6增强了AR-SRC-1的相互作用，在50 ng / mL的浓度下诱导作用最大（P <0.05）。IL-6降低了AR-SMRT相互作用，在50 ng / mL时检测到显着降低（P <0.05）。

结论

IL-6增强LNCaP细胞增殖，这表明IL-6可能通过激活AR引起AR阳性前列腺癌的生长。IL-6诱导的AR激活的机制是通过增强AR-SRC-1相互作用和抑制AR-SMRT相互作用来介导的。我们已经显示了SRC-1和SMRT在调节IL-6诱导的AR反式激活中的重要作用。