IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9323.html
   My bibliography  Save this article

Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer

Author

Listed:
  • Zhong Chen

    (Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University College of Medicine)

  • Xun Lan

    (Stanford University)

  • Dayong Wu

    (Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University College of Medicine)

  • Benjamin Sunkel

    (Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University College of Medicine)

  • Zhenqing Ye

    (University of Texas Health Science Center at San Antonio)

  • Jiaoti Huang

    (Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA)

  • Zhihua Liu

    (State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences)

  • Steven K. Clinton

    (Ohio State University College of Medicine)

  • Victor X. Jin

    (University of Texas Health Science Center at San Antonio)

  • Qianben Wang

    (Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University College of Medicine
    State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences)

Abstract

Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC)-regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and are associated with unfavourable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR.

Suggested Citation

  • Zhong Chen & Xun Lan & Dayong Wu & Benjamin Sunkel & Zhenqing Ye & Jiaoti Huang & Zhihua Liu & Steven K. Clinton & Victor X. Jin & Qianben Wang, 2015. "Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer," Nature Communications, Nature, vol. 6(1), pages 1-8, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9323
    DOI: 10.1038/ncomms9323
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9323
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9323?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9323. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.