The transcriptional programme of the androgen receptor (AR) in prostate cancer.
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.
Cambridge University Department of Urology, Addenbrooke's Hospital and Cancer Research UK (CRUK) Cambridge Institute, Cambridge, UK.
Alastair D
AD
Lamb
Charlie E
CE
Massie
David E
DE
Neal
D059002:Androgen Receptor Antagonists / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000235:genetics; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology
C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen
ChIP; HRPC; androgen receptor (AR); mechanisms of resistance; prostate cancer; review