Androgen Receptor and Poly(ADP-ribose) Glycohydrolase Inhibition Increases Efficiency of Androgen Ablation in Prostate Cancer Cells.

ABSTRACT: There is mounting evidence of androgen receptor signaling inducing genome instability and changing DNA repair capacity in prostate cancer cells. Expression of genes associated with base excision repair (BER) is increased with prostate cancer progression and correlates with poor prognosis. Poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) are key enzymes in BER that elongate and degrade PAR polymers on target proteins. While PARP inhibitors have been tested in clinical trials and are a promising therapy for prostate cancer patients with TMPRSS2-ERG fusions and mutations in DNA repair genes, PARG inhibitors have not been evaluated. We show that PARG is a direct androgen receptor (AR) target gene. AR is recruited to the PARG locus and induces PARG expression. Andro

SUBMITTER: Zhang M 

PROVIDER: S-EPMC7052214 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature