Androgen Receptor Tumor Suppressor Function Is Mediated by Recruitment of Retinoblastoma Protein.
Cell Rep
; 17(4): 966-976, 2016 10 18.
Article
in En
| MEDLINE
| ID: mdl-27760327
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Androgen
/
Genes, Tumor Suppressor
/
Retinoblastoma Protein
Limits:
Humans
/
Male
Language:
En
Journal:
Cell Rep
Year:
2016
Document type:
Article
Affiliation country:
United States