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Oncogene. 2018 Jan 18;37(3):313-322. doi: 10.1038/onc.2017.330. Epub 2017 Sep 18.

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

Author information

1
Division of Oncogenomics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
2
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
4
Faculty of EEMCS, Delft University of Technology, Delft, The Netherlands.
5
Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
6
Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, The Netherlands Proteomics Centre, Utrecht University, Utrecht, The Netherlands.
7
Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

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.

PMID:
28925401
DOI:
10.1038/onc.2017.330
[Indexed for MEDLINE]

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