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RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis

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Listed:
  • Eva Gonzalez-Suarez

    (Amgen Inc
    Present addresses: Cancer Epigenetics and Biology Program, Bellvitge Institute for Biomedical Research, 08907-L’Hospitalet de Llobregat-Barcelona, Spain (E.G.-S.); ImmunoGen Inc, Waltham, Massachusetts 02451, USA (J.P.).)

  • Allison P. Jacob

    (Amgen Inc)

  • Jon Jones

    (Amgen Inc)

  • Robert Miller

    (Amgen Inc)

  • Martine P. Roudier-Meyer

    (Amgen Inc)

  • Ryan Erwert

    (Amgen Inc)

  • Jan Pinkas

    (Amgen Inc
    Present addresses: Cancer Epigenetics and Biology Program, Bellvitge Institute for Biomedical Research, 08907-L’Hospitalet de Llobregat-Barcelona, Spain (E.G.-S.); ImmunoGen Inc, Waltham, Massachusetts 02451, USA (J.P.).)

  • Dan Branstetter

    (Amgen Inc)

  • William C. Dougall

    (Amgen Inc)

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

  • Eva Gonzalez-Suarez & Allison P. Jacob & Jon Jones & Robert Miller & Martine P. Roudier-Meyer & Ryan Erwert & Jan Pinkas & Dan Branstetter & William C. Dougall, 2010. "RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis," Nature, Nature, vol. 468(7320), pages 103-107, November.
    • Handle: RePEc:nat:nature:v:468:y:2010:i:7320:d:10.1038_nature09495
    DOI: 10.1038/nature09495
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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.
    2. Huiru Bai & Xiaoqin Liu & Meizhen Lin & Yuan Meng & Ruolan Tang & Yajing Guo & Nan Li & Michael F. Clarke & Shang Cai, 2024. "Progressive senescence programs induce intrinsic vulnerability to aging-related female breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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