Hes6 drives a critical AR transcriptional program to induce castration resistant prostate cancer through activation of an E2F1-mediated cell cycle network

ABSTRACT: Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. Here we show that Hes6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for other transcription factors including E2F1. In the clinical setting, we have uncovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted with restoration of sensitivity to castration. AR and E2F1 ChIPseq from multiple simultaneous LNCaP cell replicates with and without bicalutamide

ORGANISM(S): Homo sapiens

SUBMITTER: Silvia Halim 

PROVIDER: E-GEOD-49832 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress