Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona.
Department of Biomedical Sciences and Public Health, Section of Pathological Anatomy, Università Politecnica delle Marche, School of Medicine, United Hospitals, Ancona.
Eur J Histochem. 2020 Oct 19;64(4):3147. doi: 10.4081/ejh.2020.3147.
Ciliary neurotrophic factor (CNTF) is a member of interleukin-6 type cytokine family. The CNTF receptor complex is a heterodimer including gp130 and CNTF receptor α (CNTFRα) proteins triggering the activation of multiple intracellular signaling pathways including AKT/PI3K, MAPK/ERK and Jak/STAT pathways. At present no data are available on the localization of CNTF and CNTFRα in prostate as well as on the role of CNTF in this organ. In this study we have analyzed the localization of CNTF and CNTFRα by immunohistochemistry and we have used PWR-1E cell line as a model for normal glandular cell to investigate the role of this cytokine. Our results show that CNTF and CNTFRa are expressed in the staminal compart of the prostate and that CNTF selectively inhibits ERK pathway. In conclusion, we suggest that CNTF could be considered as key molecule to maintenance epithelium homeostasis via pERK downregulation by an autocrine mechanism. Further CNTF studies in prostate cancer could be useful to verify the potential role of this cytokine in carcinogenesis.
睫状神经营养因子 (CNTF) 是白细胞介素-6 型细胞因子家族的一员。CNTF 受体复合物是一种异二聚体,包括 gp130 和 CNTF 受体 α (CNTFRα) 蛋白,可触发包括 AKT/PI3K、MAPK/ERK 和 Jak/STAT 途径在内的多种细胞内信号通路的激活。目前尚无关于 CNTF 和 CNTFRα 在前列腺中的定位以及 CNTF 在该器官中的作用的数据。在这项研究中,我们通过免疫组织化学分析了 CNTF 和 CNTFRα 的定位,并使用 PWR-1E 细胞系作为正常腺细胞模型来研究这种细胞因子的作用。我们的结果表明,CNTF 和 CNTFRa 在前列腺的精囊区表达,并且 CNTF 选择性地抑制 ERK 通路。总之,我们认为 CNTF 可以通过自分泌机制下调 pERK 来维持上皮细胞的稳态,因此可以被视为关键分子。进一步研究 CNTF 在前列腺癌中的作用可能有助于验证这种细胞因子在致癌作用中的潜在作用。