RUNX1, a transcription factor mutated in breast cancer, controls the fate of ER-positive mammary luminal cells

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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.

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Maaike P A van Bragt

Brigham and Women's Hospital, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Xin Hu

Brigham and Women's Hospital, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Ying Xie

Brigham and Women's Hospital, Boston, United States

Competing interests
The authors declare that no competing interests exist.
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.

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