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dc.contributor.authorTanos, Tamara
dc.contributor.authorSflomos, George
dc.contributor.authorEcheverria, Pablo C.
dc.contributor.authorAyyanan, Ayyakkannu
dc.contributor.authorGutierrez, Maria
dc.contributor.authorDelaloye, Jean-Francois
dc.contributor.authorRaffoul, Wassim
dc.contributor.authorFiche, Maryse
dc.contributor.authorDougall, William
dc.contributor.authorSchneider, Pascal
dc.contributor.authorYalçın Özuysal, Özden
dc.contributor.authorBrisken, Cathrin
dc.date.accessioned2017-04-12T11:51:02Z
dc.date.available2017-04-12T11:51:02Z
dc.date.issued2013-04
dc.identifier.citationTanos, T., Sflomos, G., Echeverria, P. C., Ayyanan, A., Gutierrez, M., Delaloye, J.-F., Raffoul, W., Fiche, M., Dougall, W., Schneider, P., Yalçın Özuysal, Ö., and Brisken, C. (2013). Progesterone/RANKL is a major regulatory axis in the human breast. Science Translational Medicine, 5(182). doi:10.1126/scitranslmed.3005654en_US
dc.identifier.issn1946-6234
dc.identifier.urihttp://doi.org/10.1126/scitranslmed.3005654
dc.identifier.urihttp://hdl.handle.net/11147/5293
dc.description.abstractEstrogens and progesterones are major drivers of breast development but also promote carcinogenesis in this organ. Yet, their respective roles and the mechanisms underlying their action in the human breast are unclear. Receptor activator of nuclear factor kB ligand (RANKL) has been identified as a pivotal paracrine mediator of progesterone function in mouse mammary gland development and mammary carcinogenesis. Whether the factor has the same role in humans is of clinical interest because an inhibitor for RANKL, denosumab, is already used for the treatment of bone disease and might benefit breast cancer patients. We show that progesterone receptor (PR) signaling failed to induce RANKL in PR + breast cancer cell lines and in dissociated, cultured breast epithelial cells. In clinical specimens from healthy donors and intact breast tissue microstructures, hormone response was maintained and RANKL expression was under progesterone control, which increased RNA stability. RANKL was sufficient to trigger cell proliferation and was required for progesterone-induced proliferation. The findings were validated in vivo where RANKL protein expression in the breast epithelium correlated with serum progesterone levels and the protein was expressed in a subset of luminal cells that express PR. Thus, important hormonal control mechanisms are conserved across species, making RANKL a potential target in breast cancer treatment and prevention. Copyright 2013 by the American Association for the Advancement of Science; all rights reserved.en_US
dc.description.sponsorshipNational Center of Competence in Research Molecular Oncology, Oncosuisse (SNF-3100A0112090/SNF-31003-138065); Marie-Curie incoming fellowship; European Union (115188)en_US
dc.language.isoengen_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.relation.isversionof10.1126/scitranslmed.3005654en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectProgesterone receptoren_US
dc.subjectReceptor activator of nuclear factoren_US
dc.subjectRANKLen_US
dc.subjectRNAen_US
dc.subjectBreast epitheliumen_US
dc.subjectCancer cellsen_US
dc.titleProgesterone/RANKL is a major regulatory axis in the human breasten_US
dc.typearticleen_US
dc.contributor.authorIDTR103812en_US
dc.contributor.iztechauthorYalçın Özuysal, Özden
dc.relation.journalScience Translational Medicineen_US
dc.contributor.departmentİYTE, Fen Fakültesi, Moleküler Biyoloji ve Genetik Bölümüen_US
dc.identifier.volume5en_US
dc.identifier.issue182en_US
dc.identifier.wosWOS:000318018300008
dc.identifier.scopusSCOPUS:2-s2.0-84877748040
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


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