Activated androgen receptor accelerates angiogenesis in cutaneous neurofibroma by regulating VEGFA transcription
Activated androgen receptor accelerates angiogenesis in cutaneous neurofibroma by regulating VEGFA transcription
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DOI：
10.3892/ijo.2019.4797
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发表时间：
2019-07-01
影响因子：
5.2
通讯作者：
Shu, Maoguo
中科院分区：
文献类型：
--
作者：
Jia, Jing;Zhang, Haibao;Shu, Maoguo
越来越多的证据表明，皮肤神经纤维瘤(CNF)在青春期有明显的进展，而不是坏死。然而，参与这一过程的分子事件仍不清楚。青春期类固醇激素水平的变化导致雄激素受体(AR)表达水平的研究。在人CNF组织中，AR的表达与微血管密度呈正相关，并在体外促进内皮细胞管的形成。此外，激活的AR信号在体内和体外都能促进神经纤维瘤细胞的生长，并在体外促进管状细胞的形成。在本研究中，AR被证明直接与血管生成关键因子血管内皮生长因子A(VEGFA)的启动子结合，并随后诱导其表达。此外，AR抑制剂MDV3100下调VEGFA的表达，并取消内皮细胞募集和管状形成。综上所述，这项研究的结果表明，AR信号通过调节VEGFA转录促进了CNF中肿瘤的生长和血管生成。然而，AR是否可以被视为CNF的治疗靶点还需要进一步的研究。
Accumulating evidence has demonstrated the significant progression of cutaneous neurofibroma (cNF) without necrosis during puberty. However, the molecular events involved in this process remain unclear. The alteration of the steroid hormone levels during puberty has led to the investigation of the expression levels of the androgen receptor (AR). A positive correlation between AR expression and microvessel density has been reported in human cNF tissues in combination with enhanced endothelial cell tube formation in vitro. In addition, activated AR signaling can promote neurofibroma cell growth in vivo and in vitro and tube formation in vitro. In the present study, AR was shown to bind directly to the promoter of vascular endothelial growth factor A (VEGFA), a key factor involved in angiogenesis, and to sequentially induce its expression. Furthermore, the AR inhibitor, MDV3100, downregulated VEGFA expression and abolished endothelial cell recruitment and tube formation. Taken collectively, the findings of this study revealed that AR signaling enhanced tumor growth and angiogenesis in cNF by regulating VEGFA transcription. However, whether AR can be regarded a therapeutic target for cNF requires further investigation.