Endogenous androgen receptor proteomic profiling reveals genomic subcomplex involved in prostate tumorigenesis

S Stelloo*, E. Nevedomskaya, S.-Y. Kim, Liesbeth Hoekman, O B Bleijerveld, T Mirza, L F A Wessels, W.M. van Weerden, A F M Altelaar, A.M. Bergman, Willemijn Zwart*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners. Interestingly, three major subgroups of genomic subcomplexes were identified, where selective gain of function for AR genomic action in tumorigenesis was found, dictated by FOXA1 and HOXB13. In summary, by combining proteomic and genomic approaches we reveal subclasses of AR transcriptional complexes, differentiating normal AR behavior from the oncogenic state. In this process, the expression of AR interactors has key roles by reprogramming the AR cistrome and interactome in a genomic location-specific manner.Oncogene advance online publication, 18 September 2017; doi:10.1038/onc.2017.330.

Original languageEnglish
Pages (from-to)313–322
JournalOncogene
Volume37
DOIs
Publication statusPublished - 18 Jan 2018

Keywords

  • Journal Article

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