1. Developmental Biology
  2. Human Biology and Medicine
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RUNX1, a transcription factor mutated in breast cancer, controls the fate of ER-positive mammary luminal cells

  1. Maaike P A van Bragt
  2. Xin Hu
  3. Ying Xie
  4. Zhe Li  Is a corresponding author
  1. Brigham and Women's Hospital, United States
Research Article
  • Cited 39
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Cite this article as: eLife 2014;3:e03881 doi: 10.7554/eLife.03881

Abstract

RUNX1 encodes a RUNX family transcription factor (TF) and was recently identified as a novel mutated gene in human luminal breast cancers. We found that Runx1 is expressed in all subpopulations of murine mammary epithelial cells (MECs) except the secretory alveolar luminal cells. Conditional knockout of Runx1 in MECs by MMTV-Cre led to a decrease in luminal MECs, largely due to a profound reduction in the estrogen receptor (ER)-positive mature luminal subpopulation, a phenotype that could be rescued by loss of either Trp53 or Rb1. Mechanistically RUNX1 represses Elf5, a master regulatory TF gene for alveolar cells, and regulates mature luminal TF/co-factor genes (e.g., Foxa1 and Cited1) involved in the ER program. Collectively, our data identified a key regulator of the ER+ luminal lineage whose disruption may contribute to development of ER+ luminal breast cancer when under the background of either TP53 or RB1 loss.

Article and author information

Author details

  1. Maaike P A van Bragt

    Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xin Hu

    Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ying Xie

    Brigham and Women's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Zhe Li

    Brigham and Women's Hospital, Boston, United States
    For correspondence
    zli4@rics.bwh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) of Boston Children's Hospital (where the animals are housed) under protocol # 11-10-2034.

Reviewing Editor

  1. Elaine Fuchs, Rockefeller University, United States

Publication history

  1. Received: July 4, 2014
  2. Accepted: November 21, 2014
  3. Accepted Manuscript published: November 21, 2014 (version 1)
  4. Version of Record published: January 1, 2015 (version 2)

Copyright

© 2014, van Bragt et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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