Endogenous androgen receptor proteomic profiling reveals genomic subcomplex involved in prostate tumorigenesis
Open accessAbstract
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.
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Top gene hits included protein complexes such as PAF and proteins such as HOXB13 and GATA2 known to interact directly or indirectly with AR.
“Top gene hits included protein complexes such as PAF and proteins such as HOXB13 and GATA2 known to interact directly or indirectly with AR36 (Fig. 2c).”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [36]
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“Top gene hits included protein complexes such as PAF and proteins such as HOXB13 and GATA2 known to interact directly or indirectly with AR 36 (Fig.”
- Authors
- Stelloo, S., Nevedomskaya, E., Kim, Y., Hoekman, L., Bleijerveld, O. B., Mirza, T., Wessels, L. F. A., van Weerden, W. M., Altelaar, A. F. M., Bergman, A. M., & Zwart, W.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Stelloo, S
- Zwart, W
- Venue
- Oncogene
- Published
- 2017-09-18
- Volume
- 37
- Issue
- 3
- Pages
- 313-322
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2756240008
- Cited by
- 118
- References
- 59
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 14 · 2023: 10 · 2022: 16 · 2021: 25 · 2020: 7 · 2019: 20 · 2018: 7
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- androgen receptor, prostate cancer, FOXA1, HOXB13, LNCaP cells
- MeSH terms
- Androgens, Animals, Cell Transformation, Neoplastic, Humans, Male, Mice, Nude, Prostate, Prostatic Neoplasms, Receptors, Androgen, Gene Expression Regulation, Neoplastic, Homeodomain Proteins, Gene Expression Profiling, Xenograft Model Antitumor Assays, Genomics, Proteomics, Epigenesis, Genetic, Cell Line, Tumor, Cell Proliferation, Mice, Hepatocyte Nuclear Factor 3-alpha, Carcinogenesis
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