dc.contributor.author | Simigdala, N | |
dc.contributor.author | Pancholi, S | |
dc.contributor.author | Ribas, R | |
dc.contributor.author | Folkerd, E | |
dc.contributor.author | Liccardi, G | |
dc.contributor.author | Nikitorowicz-Buniak, J | |
dc.contributor.author | Johnston, SR | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | Martin, L-A | |
dc.date.accessioned | 2018-06-07T08:48:49Z | |
dc.date.accessioned | 2018-06-21T09:43:21Z | |
dc.date.issued | 2018-08-01 | |
dc.identifier.citation | British journal of cancer, 2018, 119 (3), pp. 313 - 322 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1892 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/s41416-018-0158-y | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 313 - 322 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGERNATURE | |
dc.relation.replaces | https://repository.icr.ac.uk/handle/internal/1753 | |
dc.relation.replaces | internal/1753 | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Neoplasms, Hormone-Dependent | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Tamoxifen | |
dc.subject | Androstenes | |
dc.subject | Receptors, Androgen | |
dc.subject | Estrogen Receptor alpha | |
dc.subject | Aromatase Inhibitors | |
dc.subject | Signal Transduction | |
dc.subject | Apoptosis | |
dc.subject | Cell Proliferation | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Mutation | |
dc.subject | Female | |
dc.subject | MCF-7 Cells | |
dc.title | Abiraterone shows alternate activity in models of endocrine resistant and sensitive disease. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-05-31 | |
rioxxterms.versionofrecord | 10.1038/s41416-018-0158-y | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 3 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 119 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Endocrine Therapy Resistance | |
icr.researchteam | Endocrinology | |
dc.contributor.icrauthor | Pancholi, Sunil | |
dc.contributor.icrauthor | Folkerd, Elizabeth | |
dc.contributor.icrauthor | Nikitorowicz-Buniak, Joanna | |
dc.contributor.icrauthor | Martin, Lesley-Ann | |