Androgen receptor-interacting protein HSPBAP1 facilitates growth of prostate cancer cells in androgen-deficient conditions

Khalid Saeed, Päivi Kristina Östling, Mari Björkman, Tuomas Mirtti, Kalle Alanen, Tiina Vesterinen, Anna Sankila, Johan Lundin, Mikael Lundin, Antti Rannikko, Stig Nordling, John-Patrick Mpindi, Pekka Kohonen, Kristiina Iljin, Olli Kallioniemi, Juha K. Rantala

Research output: Contribution to journalArticleScientificpeer-review


Hormonal therapies targeting androgen receptor (AR) are effective in prostate cancer (PCa), but often the cancers progress to
fatal castrate-resistant disease. Improved understanding of the cellular events during androgen deprivation would help to
identify survival and stress pathways whose inhibition could synergize with androgen deprivation. Toward this aim, we performed
an RNAi screen on 2,068 genes, including kinases, phosphatases, epigenetic enzymes and other druggable gene targets.
High-content cell spot microarray (CSMA) screen was performed in VCaP cells in the presence and absence of androgens
with detection of Ki67 and cleaved ADP-ribose polymerase (cPARP) as assays for cell proliferation and apoptosis. Thirty-nine
candidate genes were identified, whose silencing inhibited proliferation or induced apoptosis of VCaP cells exclusively under
androgen-deprived conditions. One of the candidates, HSPB (heat shock 27 kDa)-associated protein 1 (HSPBAP1), was confirmed
to be highly expressed in tumor samples and its mRNA expression levels increased with the Gleason grade. We found
that strong HSPBAP1 immunohistochemical staining (IHC) was associated with shorter disease-specific survival of PCa patients
compared with negative to moderate staining. Furthermore, we demonstrate that HSPBAP1 interacts with AR in the nucleus of
PCa cells specifically during androgen-deprived conditions, occupies chromatin at PSA/klk3 and TMPRSS2/tmprss2 enhancers
and regulates their expression. In conclusion, we suggest that HSPBAP1 aids in sustaining cell viability by maintaining AR signaling
during androgen-deprived conditions.
Original languageEnglish
JournalInternational Journal of Cancer
Issue number11
Pages (from-to)2535-2545
Number of pages11
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 3111 Biomedicine

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