Activated androgen receptor accelerates angiogenesis in cutaneous neurofibroma by regulating VEGFA transcription

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.