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  Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer

Schramek, D., Leibbrandt, A., Sigl, V., Kenner, L., Pospisilik, J. A., Lee, H. J., et al. (2010). Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature, 468, 98-102.

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Datensatz-Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-9757-9 Versions-Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-9759-5
Genre: Zeitschriftenartikel

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Schramek, Daniel, Autor
Leibbrandt, Andreas, Autor
Sigl, Verena, Autor
Kenner, Lukas, Autor
Pospisilik, John A.1, Autor
Lee, Heather J., Autor
Hanada, Reiko, Autor
Joshi, Purna A., Autor
Aliprantis, Antonios, Autor
Glimcher, Laurie, Autor
Pasparakis, Manolis, Autor
Kokha, Rama, Autor
Ormandy, Christopher, Autor
Widschwendter, Martin, Autor
Schett, Georg, Autor
Penninger, Josef M., Autor
Affiliations:
1Max Planck Society, ou_persistent13              

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Schlagwörter: -
 Zusammenfassung: Breast cancer is one of the most common cancers in humans and will on average affect up to one in eight women in their lifetime in the United States and Europe. The Women's Health Initiative and the Million Women Study have shown that hormone replacement therapy is associated with an increased risk of incident and fatal breast cancer. In particular, synthetic progesterone derivatives (progestins) such as medroxyprogesterone acetate (MPA), used in millions of women for hormone replacement therapy and contraceptives, markedly increase the risk of developing breast cancer. Here we show that the in vivo administration of MPA triggers massive induction of the key osteoclast differentiation factor RANKL (receptor activator of NF-κB ligand) in mammary-gland epithelial cells. Genetic inactivation of the RANKL receptor RANK in mammary-gland epithelial cells prevents MPA-induced epithelial proliferation, impairs expansion of the CD49fhi stem-cell-enriched population, and sensitizes these cells to DNA-damage-induced cell death. Deletion of RANK from the mammary epithelium results in a markedly decreased incidence and delayed onset of MPA-driven mammary cancer. These data show that the RANKL/RANK system controls the incidence and onset of progestin-driven breast cancer.

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Sprache(n): eng - English
 Datum: 2010-11-04
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 534692
 Art des Abschluß: -

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Titel: Nature
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 468 Artikelnummer: - Start- / Endseite: 98 - 102 Identifikator: -