The Androgen Receptor and VEGF: Mechanisms of Androgen-Regulated Angiogenesis in Prostate Cancer.

Prostate cancer progression is controlled by the androgen receptor and new blood vessel formation, or angiogenesis, which promotes metastatic prostate cancer growth. Angiogenesis is induced by elevated expression of vascular endothelial growth factor (VEGF). VEGF is regulated by many factors in the tumor microenvironment including lowered oxygen levels and elevated androgens. Here we review evidence delineating hormone mediated mechanisms of VEGF regulation, including novel interactions between the androgen receptor (AR), epigenetic and zinc-finger transcription factors, AR variants and the hypoxia factor, HIF-1. The relevance of describing the impact of both hormones and hypoxia on VEGF expression and angiogenesis is revealed in recent reports of clinical therapies targeting both VEGF and AR signaling pathways. A better understanding of the complexities of VEGF expression could lead to improved targeting and increased survival time for a subset of patients with metastatic castration-resistant prostate cancer.