Endogenous Androgen Receptor proteomic profiling reveals genomic subcomplex involved in prostate tumorigenesis

Androgen Receptor (AR) is a key player in prostate cancer development and progression. Here, we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify individual components of the AR transcription complex. In total, 66 known and novel AR interactors were identified in the presence of R1881, which were critically and selectively required in AR-driven prostate cancer cell proliferation. AR interactors required for LNCaP proliferation were profiled using ChIP-seq, identifying distinct genomic subcomplexes of AR interaction partners. Interestingly, three major subgroups of genomic subcomplexes were identified, where a selective gain-of-function for AR was identified in tumorigenesis, dictated by FOXA1 and HOXB13. Jointly, our study reveals subclasses of the AR transcription complex formation and composition, that is dictated by overexpression of AR-interactors, resulting in reprogramming of the AR cistrome and interactome in a genomic location-specific manner. Overall design: AR, ARID1a, BRG1, FOXA1, HOXB13, TLE3, TRIM28 and WDHD1 binding to DNA was profiled by ChIP-seq (Chromatin Immunoprecipitation) genome-wide in prostate cancer cell line LNCaP.