Regulation of androgen receptor expression by enhancer elements in prostate cancer

Androgen receptor (AR) overexpression is a key mechanism driving the development of castration-resistant prostate cancer (CRPC). This can result from multiple factors, including enhanced AR transcription and increased stability of AR mRNA and protein. In clinical CRPC samples, one cause of AR overexpression is gene amplification at the AR locus, which leads to elevated AR transcript and protein levels. In addition, increased activity or copy number of enhancer elements near the AR gene has been associated with elevated AR transcription. These regulatory regions interact with the AR gene promoter through enhancer-promoter looping, thereby enhancing AR mRNA transcription. Elucidating the role of these enhancer elements in driving AR overexpression and aberrant AR signaling may uncover new therapeutic targets for CRPC.