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dc.contributor.authorJeselsohn, R
dc.contributor.authorCornwell, M
dc.contributor.authorPun, M
dc.contributor.authorBuchwalter, G
dc.contributor.authorNguyen, M
dc.contributor.authorBango, C
dc.contributor.authorHuang, Y
dc.contributor.authorKuang, Y
dc.contributor.authorPaweletz, C
dc.contributor.authorFu, X
dc.contributor.authorNardone, A
dc.contributor.authorDe Angelis, C
dc.contributor.authorDetre, S
dc.contributor.authorDodson, A
dc.contributor.authorMohammed, H
dc.contributor.authorCarroll, JS
dc.contributor.authorBowden, M
dc.contributor.authorRao, P
dc.contributor.authorLong, HW
dc.contributor.authorLi, F
dc.contributor.authorDowsett, M
dc.contributor.authorSchiff, R
dc.contributor.authorBrown, M
dc.date.accessioned2017-05-23T15:41:53Z
dc.date.issued2017-05-15
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2017, 114 (22), pp. E4482 - E4491
dc.identifier.issn0027-8424
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/651
dc.identifier.eissn1091-6490
dc.identifier.doi10.1073/pnas.1620993114
dc.description.abstractThe estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.
dc.formatPrint-Electronic
dc.format.extentE4482 - E4491
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectBreast
dc.subjectChromatin
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectTamoxifen
dc.subjectReceptors, Estrogen
dc.subjectAntineoplastic Agents, Hormonal
dc.subjectCell Proliferation
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.subjectSOX9 Transcription Factor
dc.subjectEpithelial-Mesenchymal Transition
dc.subjectMCF-7 Cells
dc.titleEmbryonic transcription factor SOX9 drives breast cancer endocrine resistance.
dc.typeJournal Article
dcterms.dateAccepted2017-04-28
rioxxterms.versionofrecord10.1073/pnas.1620993114
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-05-15
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfProceedings of the National Academy of Sciences of the United States of America
pubs.issue22
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume114
pubs.embargo.termsNot known
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorDowsett, Mitchen
dc.contributor.icrauthorMarsden,en


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