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dc.contributor.authorSimigdala, N
dc.contributor.authorPancholi, S
dc.contributor.authorRibas, R
dc.contributor.authorFolkerd, E
dc.contributor.authorLiccardi, G
dc.contributor.authorNikitorowicz-Buniak, J
dc.contributor.authorJohnston, SR
dc.contributor.authorDowsett, M
dc.contributor.authorMartin, L-A
dc.date.accessioned2018-06-07T08:48:49Z
dc.date.accessioned2018-06-21T09:43:21Z
dc.date.issued2018-08
dc.identifier.citationBritish journal of cancer, 2018, 119 (3), pp. 313 - 322
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1892
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/s41416-018-0158-y
dc.description.abstractBackground Resistance to endocrine therapy remains a major clinical problem in the treatment of oestrogen-receptor positive (ER+) breast cancer. Studies show androgen-receptor (AR) remains present in 80-90% of metastatic breast cancers providing support for blockade of AR-signalling. However, clinical studies with abiraterone, which blocks cytochrome P450 17A1 (CYP17A1) showed limited benefit.Methods In order to address this, we assessed the impact of abiraterone on cell-viability, cell-death, ER-mediated transactivation and recruitment to target promoters. together with ligand-binding assays in a panel of ER+ breast cancer cell lines that were either oestrogen-dependent, modelling endocrine-sensitive disease, or oestrogen-independent modelling relapse on an aromatase inhibitor. The latter, harboured wild-type (wt) or naturally occurring ESR1 mutations.Results Similar to oestrogen, abiraterone showed paradoxical impact on proliferation by stimulating cell growth or death, depending on whether the cells are hormone-dependent or have undergone prolonged oestrogen-deprivation, respectively. Abiraterone increased ER-turnover, induced ER-mediated transactivation and ER-degradation via the proteasome.Conclusions Our study confirms the oestrogenic activity of abiraterone and highlights its differential impact on cells dependent on oestrogen for their proliferation vs. those that are ligand-independent and harbour wt or mutant ESR1. These properties could impact the clinical efficacy of abiraterone in breast cancer.
dc.formatPrint-Electronic
dc.format.extent313 - 322
dc.languageeng
dc.language.isoeng
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/1753
dc.relation.replacesinternal/1753
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectNeoplasms, Hormone-Dependent
dc.subjectNeoplasm Metastasis
dc.subjectNeoplasm Recurrence, Local
dc.subjectTamoxifen
dc.subjectAndrostenes
dc.subjectReceptors, Androgen
dc.subjectEstrogen Receptor alpha
dc.subjectAromatase Inhibitors
dc.subjectSignal Transduction
dc.subjectApoptosis
dc.subjectCell Proliferation
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectDrug Resistance, Neoplasm
dc.subjectMutation
dc.subjectFemale
dc.subjectMCF-7 Cells
dc.titleAbiraterone shows alternate activity in models of endocrine resistant and sensitive disease.
dc.typeJournal Article
dcterms.dateAccepted2018-05-31
rioxxterms.versionofrecord10.1038/s41416-018-0158-y
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue3
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/Endocrine Therapy Resistance
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/Endocrine Therapy Resistance
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.volume119
pubs.embargo.termsNot known
icr.researchteamEndocrine Therapy Resistanceen_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorFolkerd, Elizabethen
dc.contributor.icrauthorNikitorowicz-Buniak, Joannaen
dc.contributor.icrauthorJohnston, Stephenen
dc.contributor.icrauthorDowsett, Mitchen
dc.contributor.icrauthorPancholi, Sunilen
dc.contributor.icrauthorMartin, Lesley-Annen


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