The transcriptional programme of the androgen receptor (AR) in prostate cancer

Abstract

The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth. AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone. Current molecular techniques, such as chromatin‐immunoprecipitation sequencing (ChIP‐seq), have permitted identification of direct AR‐binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC. The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on‐going critical role of the AR throughout all stages of the disease. Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co‐factors, such as the E2F family, c‐Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors.

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

“…As confirmed by luciferase reporter gene assays, miR-124 directly binds to the 3’UTR of AR. Previous studies reported that persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-myc and signal transducer and activator of transcription (STAT) transcription factors [51]. C-myc could repress the proliferation inhibitor p27 expression which is decreased in BC tissues [52].…”

Genome-wide analysis of AR binding and comparison with transcript expression in primary human fetal prostate fibroblasts and cancer associated fibroblasts

“…Recent advances in ChIP sequencing (ChIPseq) and gene profiling technologies have enabled the characterization of genome-wide AR binding and the AR transcriptional network (reviewed in [11]). The majority of these studies have been conducted on prostate cancer cell lines and considerable effort has been made in defining AR targets in tumour epithelium [12][13][14][15][16][17].…”

Advanced prostate cancer – patient survival and potential impact of enzalutamide and other emerging therapies

“…Given that the AR transcription program remains active despite emergence of castration resistance,64 this property has been exploited to screen for anti-androgens with specific ability to bind and inhibit the AR without the agonistic effects 65…”