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dc.contributor.authorTaylor, Karen J.
dc.contributor.authorSims, Andrew H.
dc.contributor.authorLiang, Liang
dc.contributor.authorFaratian, Dana
dc.contributor.authorMuir, Morwenna
dc.contributor.authorWalker, Graeme
dc.contributor.authorKuske, Barbara
dc.contributor.authorDixon, J. Michael
dc.contributor.authorCameron, David A.
dc.contributor.authorHarrison, David J.
dc.contributor.authorLangdon, Simon P.
dc.date.accessioned2015-03-13T16:31:06Z
dc.date.available2015-03-13T16:31:06Z
dc.date.issued2010-06-22
dc.identifier.citationTaylor , K J , Sims , A H , Liang , L , Faratian , D , Muir , M , Walker , G , Kuske , B , Dixon , J M , Cameron , D A , Harrison , D J & Langdon , S P 2010 , ' Dynamic changes in gene expression in vivo predict prognosis of tamoxifen-treated patients with breast cancer ' , Breast Cancer Research , vol. 12 , no. 3 , R39 . https://doi.org/10.1186/bcr2593en
dc.identifier.issn1465-5411
dc.identifier.otherPURE: 23160079
dc.identifier.otherPURE UUID: 917ced98-d4d8-4f50-9a78-9f814338891a
dc.identifier.otherWOS: 000285689000015
dc.identifier.otherScopus: 78149490372
dc.identifier.otherORCID: /0000-0001-9041-9988/work/64034240
dc.identifier.urihttp://hdl.handle.net/10023/6237
dc.description.abstractIntroduction: Tamoxifen is the most widely prescribed anti-estrogen treatment for patients with estrogen receptor (ER)-positive breast cancer. However, there is still a need for biomarkers that reliably predict endocrine sensitivity in breast cancers and these may well be expressed in a dynamic manner. Methods: In this study we assessed gene expression changes at multiple time points (days 1, 2, 4, 7, 14) after tamoxifen treatment in the ER-positive ZR-75-1 xenograft model that displays significant changes in apoptosis, proliferation and angiogenesis within 2 days of therapy. Results: Hierarchical clustering identified six time-related gene expression patterns, which separated into three groups: two with early/transient responses, two with continuous/late responses and two with variable response patterns. The early/transient response represented reductions in many genes that are involved in cell cycle and proliferation (e.g. BUB1B, CCNA2, CDKN3, MKI67, UBE2C), whereas the continuous/late changed genes represented the more classical estrogen response genes (e.g. TFF1, TFF3, IGFBP5). Genes and the proteins they encode were confirmed to have similar temporal patterns of expression in vitro and in vivo and correlated with reduction in tumour volume in primary breast cancer. The profiles of genes that were most differentially expressed on days 2, 4 and 7 following treatment were able to predict prognosis, whereas those most changed on days 1 and 14 were not, in four tamoxifen treated datasets representing a total of 404 patients. Conclusions: Both early/transient/proliferation response genes and continuous/late/estrogen-response genes are able to predict prognosis of primary breast tumours in a dynamic manner. Temporal expression of therapy-response genes is clearly an important factor in characterising the response to endocrine therapy in breast tumours which has significant implications for the timing of biopsies in neoadjuvant biomarker studies.
dc.format.extent13
dc.language.isoeng
dc.relation.ispartofBreast Cancer Researchen
dc.rights© 2010 Taylor et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectR Medicineen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subject.lccRen
dc.subject.lccRC0254en
dc.titleDynamic changes in gene expression in vivo predict prognosis of tamoxifen-treated patients with breast canceren
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.identifier.doihttps://doi.org/10.1186/bcr2593
dc.description.statusPeer revieweden


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