Ide Hisamitsu, Lu Yan, Yu Jingsong, Noguchi Takahiro, Kanayama Mayuko, Muto Satoru, Yamaguchi Raizo, Kawato Suguru, Horie Shigeo
Department of Urology, Teikyo University School of Medicine, Tokyo, Japan.
Department of Urology, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
Hum Cell. 2017 Apr;30(2):133-139. doi: 10.1007/s13577-016-0158-2. Epub 2017 Jan 16.
There is now mounting evidence that the aryl hydrocarbon receptor (AhR) plays an important role in physiologic responses such as development, cell cycle regulation, immune function and also malignant transformation in various tissues. The strong nuclear AhR expression is observed in the invasive phenotype, and an elevated nuclear AhR expression is associated with a poor prognosis of human prostate cancer. On the other hand, there are conflicting results that the AhR deficiency results in increased susceptibility to prostate tumors in mouse model. In the present study, we investigated AhR expression and its role in the growth and invasiveness of human prostate cancer cells. The AhR protein expression was detected in prostate cancer cell lines and human prostate cancer tissues. A small interfering RNA targeting AhR, constitutive active AhR expression vector, and AhR agonist and antagonist were used to moderate its expression and signaling. The induction of AhR signaling attenuated invasiveness of prostate cancer cells without affecting the cellular growth rate. These results suggest that AhR signaling in prostate cancer cells facilitates invasion of these cells, and modulation with this signaling can be a potential therapeutic target of invasive tumors.
目前越来越多的证据表明,芳烃受体(AhR)在诸如发育、细胞周期调控、免疫功能等生理反应中发挥重要作用,并且在各种组织的恶性转化过程中也起作用。在侵袭性表型中观察到强烈的细胞核AhR表达,而细胞核AhR表达升高与人类前列腺癌的不良预后相关。另一方面,有相互矛盾的结果表明,在小鼠模型中AhR缺陷会导致对前列腺肿瘤的易感性增加。在本研究中,我们调查了AhR在人前列腺癌细胞生长和侵袭中的表达及其作用。在前列腺癌细胞系和人前列腺癌组织中检测到AhR蛋白表达。使用靶向AhR的小干扰RNA、组成型活性AhR表达载体以及AhR激动剂和拮抗剂来调节其表达和信号传导。AhR信号传导的诱导减弱了前列腺癌细胞的侵袭性,而不影响细胞生长速率。这些结果表明,前列腺癌细胞中的AhR信号传导促进了这些细胞的侵袭,并且对该信号传导进行调节可能是侵袭性肿瘤的潜在治疗靶点。