The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer
Open accessAbstract
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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Cited by
Nishimura, R., Osako, T., Nishiyama, Y., Tashima, R., Nakano, M., Fujisue, M., Toyozumi, Y., & Arima, N. (2013) · Oncology · doi:10.1159/000353099 · Cited by 13,166
Inflammation meets cancer, with NF-κB as the matchmaker
Ben-Neriah, Y., & Karin, M. (2011) · Nature Immunology · doi:10.1038/ni.2060 · Cited by 1,373
Macias, H., & Hinck, L. (2012) · WIREs Developmental Biology · doi:10.1002/wdev.35 · Cited by 849
Osteoimmunology: evolving concepts in bone–immune interactions in health and disease
Tsukasaki, M., & Takayanagi, H. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0178-8 · Cited by 771
Mechanistic Pathways of Sex Differences in Cardiovascular Disease
Regitz-Zagrosek, V., & Kararigas, G. (2017) · Physiological Reviews · doi:10.1152/physrev.00021.2015 · Cited by 732
Metadata
- Authors
- Schramek, D., Leibbrandt, A., Sigl, V., Kenner, L., Pospisilik, J. A., Lee, H. J., Hanada, R., Joshi, P. A., Aliprantis, A., Glimcher, L., Pasparakis, M., Khokha, R., Ormandy, C. J., Widschwendter, M., Schett, G., & Penninger, J. M.
- Venue
- Nature
- Published
- 2010-09-29
- Volume
- 468
- Issue
- 7320
- Pages
- 98-102
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2023398724
- Cited by
- 592
- References
- 42
- FWCI
- 30.68
- Type
- journal article
- Language
- en
- Open access
- green
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- Schramek, D., Leibbrandt, A., Sigl, V., Kenner, L., Pospisilik, J. A., Lee, H. J., Hanada, R., Joshi, P. A., Aliprantis, A., Glimcher, L., Pasparakis, M., Khokha, R., Ormandy, C. J., Widschwendter, M., Schett, G., & Penninger, J. M. (2010). Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature. https://doi.org/10.1038/nature09387
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