Aim

Androgen receptor splice variants (AR-Vs) produced by alternative splicing of the AR play an important role in the treatment resistance and progression of prostate cancer (PCa). In this study, two most common AR variants and how they associate with the inflammatory response (NF-Kβ) and regulatory transcriptional activity (HSP-27) genes were investigated in patients with PCa and metastatic PCa (Met-PCa).

Methods

Our study was carried out with the whole blood obtained from 25 healthy control subjects, 25 PCa patients and 39 Met-PCa patients. We examined the expression levels of AR, AR-V7 and AR-V567es genes via Real-time PCR and those of HSP-27 and NF-Kβ via ELISA method.

Results

AR, AR-V7 and AR-V567es expressions were observed in 84.61%, 64.1%, 23.07% of Met-PCa patients respectively. The expression levels of full-length AR and variants (AR-V7 and AR-V567es) were associated with the prostate cancer stage. In the Met-PCa, the expression levels of AR, AR-V7 and AR-V567es were associated with the Gleason Scores but not with the PSA levels. AR-V7 expression levels in stage T4 patients significantly increased. NF-Kβ and HSP-27 protein levels were significantly higher in Met-PCa patients.

Discussion

Our findings highlight the targeting of the proteostasis and inflammation pathways through inhibiting HSP-27 and NF-Kβ. This might be a valuable strategy to overcome anti-androgen resistance and improve drug therapy in Met-PCa patients whose gene expression levels of AR-V7 and AR-V567es variants are high.

中文翻译：

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前列腺癌转移中潜在调控信号分子的上调与雄激素受体剪接变体AR-V7和AR-V567es相关

目标

通过AR的可变剪接产生的雄激素受体剪接变体（AR-Vs）在前列腺癌（PCa）的治疗抗性和进展中起重要作用。在这项研究中，对PCa和转移性PCa（Met-PCa）患者研究了两种最常见的AR变体以及它们与炎症反应（NF-Kβ）和调节转录活性（HSP-27）基因的关系。

方法

我们的研究是从25位健康对照受试者，25位PCa患者和39位Met-PCa患者获得的全血中进行的。我们通过实时PCR检测了AR，AR-V7和AR-V567es基因的表达水平，并通过ELISA方法检测了HSP-27和NF-Kβ的表达水平。

结果

在Met-PCa患者中分别观察到AR，AR-V7和AR-V567es表达，分别为84.61％，64.1％，23.07％。全长AR及其变体（AR-V7和AR-V567es）的表达水平与前列腺癌分期有关。在Met-PCa中，AR，AR-V7和AR-V567es的表达水平与格里森评分相关，而与PSA水平无关。T4期患者的AR-V7表达水平显着升高。Met-PCa患者的NF-Kβ和HSP-27蛋白水平显着升高。

讨论区

我们的发现强调了通过抑制HSP-27和NF-Kβ来靶向蛋白质稳定和炎症途径。对于AR-V7和AR-V567es变体的基因表达水平较高的Met-PCa患者，这可能是克服抗雄激素耐药性并改善药物治疗的有价值的策略。