GREB1 amplifies androgen receptor output in human prostate cancer and contributes to antiandrogen resistance.

ABSTRACT: Genomic amplification of the androgen receptor (AR) is an established mechanism of antiandrogen resistance in prostate cancer. Here, we show that the magnitude of AR signaling output, independent of AR genomic alteration or expression level, also contributes to antiandrogen resistance, through upregulation of the coactivator GREB1. We demonstrate 100-fold heterogeneity in AR output within human prostate cancer cell lines and show that cells with high AR output have reduced sensitivity to enzalutamide. Through transcriptomic and shRNA knockdown studies, together with analysis of clinical datasets, we identify GREB1 as a gene responsible for high AR output. We show that GREB1 is an AR target gene that amplifies AR o

SUBMITTER: Lee E 

PROVIDER: S-EPMC6336405 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature