Abstract

<div>Abstract<p>Males have a higher incidence of renal cell carcinoma (RCC) than females, but the reason for this gender difference is unknown. Addressing this question, we report the discovery of an androgen receptor (AR)–induced HIF2α/VEGF signal that drives RCC progression. AR attenuation or augmentation in RCC cells altered their proliferation, migration, and invasion in multiple models <i>in vitro</i> and <i>in vivo</i>. Mechanistic investigations revealed that AR targeting inhibited RCC cell migration and invasion by modulating HIF2α/VEGF signals at the level of mRNA and protein expression. Interrupting HIF2α/VEGF signals with inhibitors of either HIF2α or VEGF was sufficient to suppress RCC progression. Similarly, the specific AR degradation enhancer ASC-J9 was sufficient to suppress AR-induced HIF2α/VEGF signaling and RCC progression in multiple models <i>in vitro</i> and <i>in vivo</i>. Taken together, our results revealed a novel role for AR in RCC initiation and progression with implications for novel therapeutic strategies. <i>Cancer Res; 74(16); 4420–30. ©2014 AACR</i>.</p></div>

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.