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dc.date.accessioned2018-06-06T11:46:47Z
dc.date.available2018-06-06T11:46:47Z
dc.date.issued2018-01en_US
dc.identifierhttps://www.nature.com/articles/s41419-017-0035-2.pdfen_US
dc.identifier.citationCELL DEATH & DISEASE, 2018, 9en_US
dc.identifier.issn2041-4889en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1750
dc.description.abstractAnalysis of publicly available genomic and gene expression data demonstrates that MCL1 expression is frequently elevated in breast cancer. Distinct from other pro-survival Bcl-2 family members, the short half-life of MCL-1 protein led us to investigate MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data. Here, we report associations between high MCL-1 and poor prognosis in specific subtypes of breast cancer including triple-negative breast cancer, an aggressive form that lacks targeted treatment options. Deletion of MCL-1 in the mammary epithelium of genetically engineered mice revealed an absolute requirement for MCL-1 in breast tumorigenesis. The clinical applicability of these findings was tested through a combination of approaches including knock-down or inhibition of MCL-1 to show triple-negative breast cancer cell line dependence on MCL-1 in vitro and in vivo. Our data demonstrate that high MCL-1 protein expression is associated with poor outcome in breast cancer and support the therapeutic targeting of MCL-1 in this disease.en_US
dc.subjectsmall-molecule inhibitor anti-apoptotic mcl-1 bh3 mimetic abt-737 antiapoptotic mcl-1 survival factor image-analysis cell-survival mouse model bcl-2 expression Cell Biologyen_US
dc.titleMCL-1 is a prognostic indicator and drug target in breast canceren_US
dc.typeJournal Article
rioxxterms.licenseref.startdate2018-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCELL DEATH & DISEASEen_US
pubs.declined2018-06-06T12:37:13.64+0100
pubs.notesISI Document Delivery No.: FZ1ON Times Cited: 0 Cited Reference Count: 56 Campbell, Kirsteen J. Dhayade, Sandeep Ferrari, Nicola Sims, Andrew H. Johnson, Emma Mason, Susan M. Dickson, Ashley Ryan, Kevin M. Kalna, Gabriela Edwards, Joanne Tait, Stephen W. G. Blyth, Karen Campbell, Kirsteen/0000-0002-0201-8736 Breast Cancer Now pilot grant [2014MaySP321, 2015NovSPR589]; Royal Society Dorothy Hodgkin Fellowship; CRUK [C596/A17196]; Breast Cancer Now; Royal Society; CRUK We wish to thank Jane Hair and NHS Greater Glasgow and Clyde Biorepository for TMA access; and Histology services and the BSU facilities at the CRUK Beatson Institute (C596/A18076 & C596/A17196). We thank Prof W.J. Muller for MMTV-cre mice and Prof Hans Jorg Fehling and the European Mouse Mutant Archive (EMMA) for providing the Rosa-tdRFP mice. This work was funded by a Breast Cancer Now pilot grant 2014MaySP321 (K.B., K.J.C.) and project grant 2015NovSPR589 (S.W.G.T., K.J.C., K.B.); Royal Society Dorothy Hodgkin Fellowship (K.J.C.) and CRUK core funding C596/A17196 (K.B. lab). We thank members of the Blyth and Tait labs for discussion and input and Catherine Winchester, Alessandra Riggio and Catherine Cloix for critical reading of this manuscript. This work is supported by funds from Breast Cancer Now, The Royal Society and CRUK. 0 Nature publishing group Londonen_US
pubs.notesNot knownen_US
pubs.volume9en_US
pubs.embargo.termsNot knownen_US
pubs.oa-locationhttps://www.nature.com/articles/s41419-017-0035-2.pdfen_US


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