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

Daniel Schramek, Andreas Leibbrandt, Verena Sigl, Lukas Kenner, John A. Pospisilik, Heather J. Lee, Reiko Hanada, Purna A. Joshi, Antonios Aliprantis, Laurie Glimcher, Manolis Pasparakis, Rama Khokha, Christopher J. Ormandy, Martin Widschwendter, Georg Schett and Josef M. Penninger ()
Additional contact information
Daniel Schramek: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Andreas Leibbrandt: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Verena Sigl: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Lukas Kenner: Medical University of Vienna
John A. Pospisilik: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Heather J. Lee: Garvan Institute of Medical Research, Darlinghurst 2010, Sydney, Australia
Reiko Hanada: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Purna A. Joshi: Ontario Cancer Institute, University of Toronto, Toronto, Ontario M5G 2M9, Canada
Antonios Aliprantis: Harvard School of Public Health, Harvard Medical School and the Ragon Institute of MGH/MIT and Harvard
Laurie Glimcher: Harvard School of Public Health, Harvard Medical School and the Ragon Institute of MGH/MIT and Harvard
Manolis Pasparakis: Institute for Genetics, Centre for Molecular Medicine (CMMC), and Cologne Excellence Cluster (CECAD), University of Cologne, Zülpicher Strasse 47a, 50674 Cologne, Germany
Rama Khokha: Ontario Cancer Institute, University of Toronto, Toronto, Ontario M5G 2M9, Canada
Christopher J. Ormandy: Garvan Institute of Medical Research, Darlinghurst 2010, Sydney, Australia
Martin Widschwendter: University College London, London WC1E 6AU, UK
Georg Schett: University of Erlangen-Nuremberg
Josef M. Penninger: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences

Nature, 2010, vol. 468, issue 7320, 98-102

Abstract: Progestins and breast cancer Progestins, used in contraceptives and hormone replacement therapy, have been linked to breast cancer. Two teams working independently have now found a mechanistic basis for this association. Schramek et al. show in a mouse model that synthetic progestins can promote mammary tumour formation by inducing the osteoclast differentiation factor RANKL, which acts on mammary epithelial cells through the RANKL receptor RANK. Gonzalez-Suarez et al. find that inhibition of RANKL reduces tumorigenesis in hormone-induced as well as in other mouse mammary gland tumour models, suggesting a new therapeutic approach. One RANKL inhibitor (denosumab) is in clinical trials as a treatment for bone loss in post-menopausal osteoporosis and for the treatment of skeletal-related symptoms in metastatic bone disease.

Date: 2010
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DOI: 10.1038/nature09387

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