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Type: Journal article
Title: Expression of androgen receptor splice variants in clinical breast cancers
Author: Hickey, T.
Irvine, C.
Dvinge, H.
Tarulli, G.
Hanson, A.
Ryan, N.
Pickering, M.
Birrell, S.
Hu, D.
Mackenzie, P.
Russell, R.
Caldas, C.
Raj, G.
Dehm, S.
Plymate, S.
Bradley, R.
Tilley, W.
Selth, L.
Citation: Oncotarget, 2015; 6(42):44728-44744
Publisher: Impact Journals
Issue Date: 2015
ISSN: 1949-2553
Statement of
Theresa E. Hickey, Connie M. Irvine, Heidi Dvinge, Gerard A. Tarulli, Adrienne R. Hanson, Natalie K. Ryan, Marie A. Pickering, Stephen N. Birrell, Dong Gui Hu, Peter I. Mackenzie, Roslin Russell, Carlos Caldas, Ganesh V. Raj, Scott M. Dehm, Stephen R. Plymate, Robert K. Bradley, Wayne D. Tilley, Luke A. Selth
Abstract: The importance of androgen receptor (AR) signaling is increasingly being recognized in breast cancer, which has elicited clinical trials aimed at assessing the efficacy of androgen deprivation therapy (ADT) for metastatic disease. In prostate cancer, resistance to ADT is frequently associated with the emergence of androgen-independent splice variants of the AR (AR variants, AR-Vs) that lack the LBD and are constitutively active. Women with breast cancer may be prone to a similar phenomenon. Herein, we show that in addition to the prototypical transcript, the <i>AR</i> gene produces a diverse range of AR-V transcripts in primary breast tumors. The most frequently and highly expressed variant was AR-V7 (exons 1/2/3/CE3), which was detectable at the mRNA level in &#x003E; 50% of all breast cancers and at the protein level in a subset of ER&#x03B1;-negative tumors. Functionally, AR-V7 is a constitutively active and ADT-resistant transcription factor that promotes growth and regulates a transcriptional program distinct from AR in ER&#x03B1;-negative breast cancer cells. Importantly, we provide <i>ex vivo</i> evidence that AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors. These findings have implications for treatment response in the ongoing clinical trials of ADT in breast cancer.
Keywords: androgen receptor; breast cancer; androgen deprivation therapy; alternative splicing; biomarker
Description: Published: November 05, 2015
Rights: Creative Commons License. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. PII: 6296
DOI: 10.18632/oncotarget.6296
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