The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer | Zendy

Naomi L. Sharma | Zendy; Charles Massie | Zendy; Falk Butter | Zendy; Matthias Mann | Zendy; Hélène Bon | Zendy; Antonio RamosMontoya | Zendy; Suraj Me | Zendy; Rory Stark | Zendy; Alastair Lamb | Zendy; Helen E. Scott | Zendy; Anne Y. Warren | Zendy; David E. Neal | Zendy; Ian G. Mills | Zendy

Open Access

The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer

Author(s) -

Naomi L. Sharma,

Charles Massie,

Falk Butter,

Matthias Mann,

Hélène Bon,

Antonio RamosMontoya,

Suraj Me,

Rory Stark,

Alastair Lamb,

Helen E. Scott,

Anne Y. Warren,

David E. Neal,

Ian G. Mills

Publication year - 2014

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/gku281

Subject(s) - androgen receptor , biology , prostate cancer , transcription factor , cancer research , phenotype , ets transcription factor family , gene , chromoplexy , androgen , promoter , genetics , gene expression , cancer , endocrinology , hormone , pca3

In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention.

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