Research Papers:

MED1 mediates androgen receptor splice variant induced gene expression in the absence of ligand

Gang Liu _, Cynthia Sprenger, Pin-Jou Wu, Shihua Sun, Takuma Uo, Kathleen Haugk, Kathryn Soriano Epilepsia and Stephen Plymate

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Oncotarget. 2015; 6:288-304. https://doi.org/10.18632/oncotarget.2672

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Gang Liu1, Cynthia Sprenger1,2, Pin-Jou Wu1, Shihua Sun1, Takuma Uo1, Kathleen Haugk2, Kathryn Soriano Epilepsia1, Stephen Plymate1,2

1Department of Medicine, University of Washington, Seattle 98104, WA, USA

2Veteran Affairs Puget Sound Health Care System, Seattle 98104, WA, USA

Correspondence to:

Stephen Plymate, e-mail: [email protected]

Keywords: prostate cancer, androgen receptor splice variant, ARv567es, MED1, UBE2C

Received: July 01, 2014     Accepted: November 02, 2014     Published: January 28, 2015


The appearance of constitutively active androgen receptor splice variants (AR-Vs) has been proposed as one of the causes of castration-resistant prostate cancer (CRPC). However, the underlying mechanism of AR-Vs in CRPC transcriptional regulation has not been defined. A distinct transcriptome enriched with cell cycle genes, e.g. UBE2C, has been associated with AR-Vs, which indicates the possibility of an altered transcriptional mechanism when compared to full-length wild-type AR (ARfl). Importantly, a recent study reported the critical role of p-MED1 in enhancing UBE2C expression through a locus looping pattern, which only occurs in CRPC but not in androgen-dependent prostate cancer (ADPC). To investigate the potential correlation between AR-V and MED1, in the present study we performed protein co-immunoprecipitation, chromatin immunoprecipitation, and cell proliferation assays and found that MED1 is necessary for ARv567es induced UBE2C up-regulation and subsequent prostate cancer cell growth. Furthermore, p-MED1 is bound to ARv567es independent of full-length AR; p-MED1 has higher recruitment to UBE2C promoter and enhancer regions in the presence of ARv567es. Our data indicate that p-MED1 serves as a key mediator in ARv567es induced gene expression and suggests a mechanism by which AR-Vs promote the development and progression of CRPC.

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