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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & R, 2010. "Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer," Nature, Nature, vol. 468(7320), pages 98-102, November.
    • Handle: RePEc:nat:nature:v:468:y:2010:i:7320:d:10.1038_nature09387
    DOI: 10.1038/nature09387
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    Cited by:

    1. Ana Sofia Rocha & Alejandro Collado-Solé & Osvaldo Graña-Castro & Jaime Redondo-Pedraza & Gonzalo Soria-Alcaide & Alex Cordero & Patricia G. Santamaría & Eva González-Suárez, 2023. "Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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