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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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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-9757-9 Version Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-9759-5
Genre: Journal Article

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

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 Abstract: 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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Language(s): eng - English
 Dates: 2010-11-04
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 534692
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Title: Nature
Source Genre: Journal
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Pages: - Volume / Issue: 468 Sequence Number: - Start / End Page: 98 - 102 Identifier: -