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Title: Progesterone/RANKL is a major regulatory axis in the human breast
Authors: Tanos, Tamara
Sflomos, George
Echeverria, Pablo C.
Ayyanan, Ayyakkannu
Gutierrez, Maria
Delaloye, Jean-Francois
Raffoul, Wassim
Fiche, Maryse
Dougall, William
Schneider, Pascal
Yalçın Özuysal, Özden
Brisken, Cathrin
Keywords: Progesterone receptor
Receptor activator of nuclear factor
Breast epithelium
Cancer cells
Publisher: American Association for the Advancement of Science
Source: Tanos, 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.3005654
Abstract: Estrogens 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.
ISSN: 1946-6234
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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