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dc.contributor.authorFaratian, Dana
dc.contributor.authorSims, Andrew H.
dc.contributor.authorMullen, Peter
dc.contributor.authorKay, Charlene
dc.contributor.authorUm, Inhwa
dc.contributor.authorLangdon, Simon P.
dc.contributor.authorHarrison, David J.
dc.date.accessioned2013-11-05T11:01:10Z
dc.date.available2013-11-05T11:01:10Z
dc.date.issued2011-08-31
dc.identifier.citationFaratian , D , Sims , A H , Mullen , P , Kay , C , Um , I , Langdon , S P & Harrison , D J 2011 , ' Sprouty 2 is an independent prognostic factor in breast cancer and may be useful in stratifying patients for trastuzumab therapy ' PLoS One , vol. 6 , no. 8 , e23772 , pp. - . https://doi.org/10.1371/journal.pone.0023772en
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 23159402
dc.identifier.otherPURE UUID: c72ad816-acfa-4112-aaab-b0bdf0321fb2
dc.identifier.otherWOS: 000294680800020
dc.identifier.otherScopus: 80052332155
dc.identifier.urihttp://hdl.handle.net/10023/4157
dc.description.abstractBackground: Resistance to trastuzumab is a clinical problem, partly due to overriding activation of MAPK/PI3K signalling. Sprouty-family proteins are negative regulators of MAPK/PI3K signalling, but their role in HER2-therapy resistance is unknown. Patients and Methods: Associations between Sprouty gene expression and clinicopathological features were investigated in a breast cancer microarray meta-analysis. Changes in expression of Spry2 and feedback inhibition on trastuzumab resistance were studied in SKBr3 and BT474 breast carcinoma cell lines using cell viability assays. Spry2 protein expression was measured by quantitative immunofluorescence in a cohort of 122 patients treated with trastuzumab. Results: Low gene expression of Spry2 was associated with increased pathological grade, high HER2 expression, and was a significant independent prognostic factor. Overexpression of Spry2 in SKBr3s resulted in enhanced inhibition of cell viability after trastuzumab treatment, and the PI3K-inhibitor LY294002 had a similar effect. Low Spry2 expression was associated with increased risk of death (HR = 2.28, 95% CI 1.22-4.26; p = 0.008) in trastuzumab-treated patients, including in multivariate analysis. Stratification of trastuzumab-treated patients using PTEN and Spry2 was superior to either marker in isolation. Conclusion: In breast cancers with deficient feedback inhibition, combinatorial therapy with negative regulators of growth factor signalling may be an effective therapeutic strategy.
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofPLoS Oneen
dc.rights© 2011 Faratian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectTrastuzumaben
dc.subjectBreast canceren
dc.subjectProtein expressionen
dc.subjectGene expressionen
dc.subjectBiomarkersen
dc.subjectR Medicineen
dc.subject.lccRen
dc.titleSprouty 2 is an independent prognostic factor in breast cancer and may be useful in stratifying patients for trastuzumab therapyen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0023772
dc.description.statusPeer revieweden


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