Androgen Receptor Tumor Suppressor Function Is Mediated by Recruitment of Retinoblastoma Protein

Cell Rep. 2016 Oct 18;17(4):966-976. doi: 10.1016/j.celrep.2016.09.064.


Although well characterized as a transcriptional activator that drives prostate cancer (PCa) growth, androgen receptor (AR) can function as a transcriptional repressor, and high-level androgens can suppress PCa proliferation. The molecular basis for this repression activity remains to be determined. Genes required for DNA replication are highly enriched among androgen-repressed genes, and AR is recruited to the majority of these genes, where it rapidly represses their transcription. This activity is enhanced in PCa cells expressing high AR levels and is mediated by recruitment of hypophosphorylated retinoblastoma protein (Rb). Significantly, AR also indirectly increases the expression of DNA replication genes through stimulatory effects on other metabolic genes with subsequent CDK activation and Rb hyperphosphorylation. In castration-resistant PCa cells, which are dependent on high-level AR expression, this anti-proliferative repression function might be exploited through treatment with androgen in combination with agents that suppress AR-driven metabolic functions or cell cycle progression.

Keywords: AR; DNA damage repair; DNA replication; E2F1; Rb; Retinoblastoma protein; androgen deprivation therapy; androgen receptor; metabolism; prostate cancer; transcriptional repression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgens / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinases / metabolism
  • DNA Replication / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Male
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms, Castration-Resistant
  • Receptors, Androgen / metabolism*
  • Retinoblastoma Protein / metabolism*
  • Transcription, Genetic


  • AR protein, human
  • Androgens
  • Receptors, Androgen
  • Retinoblastoma Protein
  • Cyclin-Dependent Kinases