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dc.contributor.authorHickey, TE
dc.contributor.authorIrvine, CM
dc.contributor.authorDvinge, H
dc.contributor.authorTarulli, GA
dc.contributor.authorHanson, AR
dc.contributor.authorRyan, NK
dc.contributor.authorPickering, MA
dc.contributor.authorBirrell, SN
dc.contributor.authorHu, DG
dc.contributor.authorMackenzie, PI
dc.contributor.authorRussell, R
dc.contributor.authorCaldas, C
dc.contributor.authorRaj, GV
dc.contributor.authorDehm, SM
dc.contributor.authorPlymate, SR
dc.contributor.authorBradley, RK
dc.contributor.authorTilley, WD
dc.contributor.authorSelth, LA
dc.date.accessioned2021-02-05T00:33:30Z
dc.date.available2021-02-05T00:33:30Z
dc.date.issued2015-12-29
dc.identifierpii: 6296
dc.identifier.citationHickey, T. E., Irvine, C. M., Dvinge, H., Tarulli, G. A., Hanson, A. R., Ryan, N. K., Pickering, M. A., Birrell, S. N., Hu, D. G., Mackenzie, P. I., Russell, R., Caldas, C., Raj, G. V., Dehm, S. M., Plymate, S. R., Bradley, R. K., Tilley, W. D. & Selth, L. A. (2015). Expression of androgen receptor splice variants in clinical breast cancers. ONCOTARGET, 6 (42), pp.44728-44744. https://doi.org/10.18632/oncotarget.6296.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/260054
dc.description.abstractThe 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 AR 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 > 50% of all breast cancers and at the protein level in a subset of ERα-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 ERα-negative breast cancer cells. Importantly, we provide ex vivo 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.
dc.languageEnglish
dc.publisherIMPACT JOURNALS LLC
dc.titleExpression of androgen receptor splice variants in clinical breast cancers
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.6296
melbourne.affiliation.departmentSchool of BioSciences
melbourne.affiliation.facultyScience
melbourne.source.titleOncotarget
melbourne.source.volume6
melbourne.source.issue42
melbourne.source.pages44728-44744
dc.rights.licenseCC BY
melbourne.elementsid1084471
melbourne.contributor.authorTarulli, Gerard
dc.identifier.eissn1949-2553
melbourne.accessrightsOpen Access


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