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dc.contributor.authorShamseddin, M
dc.contributor.authorDe Martino, F
dc.contributor.authorConstantin, C
dc.contributor.authorScabia, V
dc.contributor.authorLancelot, A-S
dc.contributor.authorLaszlo, C
dc.contributor.authorAyyannan, A
dc.contributor.authorBattista, L
dc.contributor.authorRaffoul, W
dc.contributor.authorGailloud-Matthieu, M-C
dc.contributor.authorBucher, P
dc.contributor.authorFiche, M
dc.contributor.authorAmbrosini, G
dc.contributor.authorSflomos, G
dc.contributor.authorBrisken, C
dc.date.accessioned2021-08-12T09:05:47Z
dc.date.available2021-08-12T09:05:47Z
dc.identifier.citationEMBO molecular medicine, 2021, 13 (7), pp. e14314 - ?
dc.identifier.issn1757-4676
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4742
dc.identifier.eissn1757-4684
dc.identifier.eissn1757-4684en_US
dc.identifier.doi10.15252/emmm.202114314
dc.identifier.doi10.15252/emmm.202114314en_US
dc.description.abstractHormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progesterone and progestins affect the breast epithelium is poorly understood because we lack adequate models to study this. We hypothesized that individual progestins differentially affect breast epithelial cell proliferation and hence breast cancer risk. Using mouse mammary tissue ex vivo, we show that testosterone-related progestins induce the PR target and mediator of PR signaling-induced cell proliferation receptor activator of NF-κB ligand (Rankl), whereas progestins with anti-androgenic properties in reporter assays do not. We develop intraductal xenografts of human breast epithelial cells from 36 women, show they remain hormone-responsive and that progesterone and the androgenic progestins, desogestrel, gestodene, and levonorgestrel, promote proliferation but the anti-androgenic, chlormadinone, and cyproterone acetate, do not. Prolonged exposure to androgenic progestins elicits hyperproliferation with cytologic changes. Androgen receptor inhibition interferes with PR agonist- and levonorgestrel-induced RANKL expression and reduces levonorgestrel-driven cell proliferation. Thus, different progestins have distinct biological activities in the breast epithelium to be considered for more informed choices in hormonal contraception.
dc.formatPrint-Electronic
dc.format.extente14314 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleContraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation.
dc.typeJournal Article
dcterms.dateAccepted2021-04-23
rioxxterms.versionVoR
rioxxterms.versionofrecord10.15252/emmm.202114314
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
dc.relation.isPartOfEMBO molecular medicine
pubs.issue7
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 control mechanisms
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 control mechanisms
pubs.publication-statusPublished
pubs.volume13en_US
pubs.embargo.termsNot known
icr.researchteamEndocrine control mechanisms
icr.researchteamEndocrine control mechanismsen_US
dc.contributor.icrauthorBrisken, Cathrinen


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