Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/91447
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dc.contributor.authorLeach, D.en
dc.contributor.authorNeed, E.en
dc.contributor.authorToivanen, R.en
dc.contributor.authorTrotta, A.en
dc.contributor.authorPalenthorpe, H.en
dc.contributor.authorTamblyn, D.en
dc.contributor.authorKopsaftis, T.en
dc.contributor.authorEngland, G.en
dc.contributor.authorSmith, E.en
dc.contributor.authorDrew, P.en
dc.contributor.authorPinnock, C.en
dc.contributor.authorLee, P.en
dc.contributor.authorHolst, J.en
dc.contributor.authorRisbridger, G.en
dc.contributor.authorChopra, S.en
dc.contributor.authorDeFranco, D.en
dc.contributor.authorTaylor, R.en
dc.contributor.authorBuchanan, G.en
dc.date.issued2015en
dc.identifier.citationOncotarget, 2015; 6(18):16135-16150en
dc.identifier.issn1949-2553en
dc.identifier.issn1949-2553en
dc.identifier.urihttp://hdl.handle.net/2440/91447-
dc.description.abstractAndrogen receptor (AR) signaling in stromal cells is important in prostate cancer, yet the mechanisms underpinning stromal AR contribution to disease development and progression remain unclear. Using patient-matched benign and malignant prostate samples, we show a significant association between low AR levels in cancer associated stroma and increased prostate cancer-related death at one, three and five years post-diganosis, and in tissue recombination models with primary prostate cancer cells that low stromal AR decreases castration-induced apoptosis. AR-regulation was found to be different in primary human fibroblasts isolated from adjacent to cancerous and non-cancerous prostate epithelia, and to represent altered activation of myofibroblast pathways involved in cell cycle, adhesion, migration, and the extracellular matrix (ECM). Without AR signaling, the fibroblast-derived ECM loses the capacity to promote attachment of both myofibroblasts and cancer cells, is less able to prevent cell-matrix disruption, and is less likely to impede cancer cell invasion. AR signaling in prostate cancer stroma appears therefore to alter patient outcome by maintaining an ECM microenvironment inhibitory to cancer cell invasion. This paper provides comprehensive insight into AR signaling in the non-epithelial prostate microenvironment, and a resource from which the prognostic and therapeutic implications of stromal AR levels can be further explored.en
dc.description.statementofresponsibilityDamien A. Leach, Eleanor F. Need, Roxanne Toivanen, Andrew P. Trotta, Helen M. Palenthorpe, David J. Tamblyn, Tina Kopsaftis, Georgina M. England, Eric Smith, Paul A. Drew, Carole B. Pinnock, Peng Lee, Jeff Holst, Gail P. Risbridger, Samarth Chopra, Donald B. DeFranco, Renea A. Taylor and Grant Buchananen
dc.language.isoenen
dc.publisherImpact Journalsen
dc.rightsAll site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. PII: 3178en
dc.subjectprostate cancer; androgen receptor; stroma; fibroblasts; extracellular matrixen
dc.titleStromal androgen receptor regulates the composition of the microenvironment to influence prostate cancer outcomeen
dc.typeJournal articleen
dc.identifier.rmid0030029234en
dc.identifier.doi10.18632/oncotarget.3873en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/606492en
dc.identifier.pubid186534-
pubs.library.collectionMedicine publicationsen
pubs.library.teamDS08en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidTamblyn, D. [0000-0002-6382-3886]en
dc.identifier.orcidSmith, E. [0000-0003-2958-3492]en
dc.identifier.orcidDrew, P. [0000-0001-5661-4771]en
Appears in Collections:Medicine publications

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