2017
DOI: 10.3390/cancers9040032
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The Androgen Receptor and VEGF: Mechanisms of Androgen-Regulated Angiogenesis in Prostate Cancer

Abstract: 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 re… Show more

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Cited by 63 publications
(54 citation statements)
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“…Thus, the activation mechanism through classical or nonclassical pathway has not been resolved too (Smith & Walker, ). The latest study found that the production of androgen‐induced VEGF was regulated by the AR complex which was formed by the Sp1 of the PCa cell central promoter region, rather than play a role by combining the ARE‐binding site of the distal VEGF promoter (Eisermann & Fraizer, ). The results of this study showed that AR expression in the BPH group was significantly higher than that in PCa and BPH+HP groups, which suggest that AR expression may play an important role in the early stage of PCa.…”
Section: Discussionmentioning
confidence: 99%
“…Thus, the activation mechanism through classical or nonclassical pathway has not been resolved too (Smith & Walker, ). The latest study found that the production of androgen‐induced VEGF was regulated by the AR complex which was formed by the Sp1 of the PCa cell central promoter region, rather than play a role by combining the ARE‐binding site of the distal VEGF promoter (Eisermann & Fraizer, ). The results of this study showed that AR expression in the BPH group was significantly higher than that in PCa and BPH+HP groups, which suggest that AR expression may play an important role in the early stage of PCa.…”
Section: Discussionmentioning
confidence: 99%
“…In addition to lowered oxygen, elevated androgens have also been found to play a crucial role in upregulating VEGF-A levels [262]. Mechanistically, it seems that the activated androgen receptor binds to Sp1 (a zinc-finger transcription factor that specifically interacts with GC-rich promoter regions) and the resulting complex then binds to the core promoter region of the VEGF-A gene, inducing its transcription [263].…”
Section: Prostate Cancermentioning
confidence: 99%
“…Among these, the use of multi-targeted RTKI and decoy receptors are considered the most promising approaches for anti-angiogenic drug discovery. Combination of antiangiogenic agents opens a new horizon for better efficacy and less toxicity of anticancer drugs [199] , [200] , [201] . On the other hand, anti-angiogenic vaccines seem to have weak potential for the development of marketed drugs due to the excessive risk of debilitating adverse effects, such as autoimmune diseases.…”
Section: Conclusion and Future Perspectivesmentioning
confidence: 99%