Transcriptional repression by androgen receptor: roles in castration-resistant prostate cancer
Year: 2019
Type: review
Abstract: Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.
Source: Asian Journal of Andrology
Authors: Jindan Yu, Galina Gritsina, Wei-Qiang Gao
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $711
OpenAlex ID: W2929595741