GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland

Cell. 2006 Dec 1;127(5):1041-55. doi: 10.1016/j.cell.2006.09.048.

Abstract

The GATA family of transcription factors plays fundamental roles in cell-fate specification. However, it is unclear if these genes are necessary for the maintenance of cellular differentiation after development. We identified GATA-3 as the most highly enriched transcription factor in the mammary epithelium of pubertal mice. GATA-3 was found in the luminal cells of mammary ducts and the body cells of terminal end buds (TEBs). Upon conditional deletion of GATA-3, mice exhibited severe defects in mammary development due to failure in TEB formation during puberty. After acute GATA-3 loss, adult mice exhibited undifferentiated luminal cell expansion with basement-membrane detachment, which led to caspase-mediated cell death in the long term. Further, FOXA1 was identified as a downstream target of GATA-3 in the mammary gland. This suggests that GATA-3 actively maintains luminal epithelial differentiation in the adult mammary gland, which raises important implications for the pathogenesis of breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Cell Differentiation*
  • Cell Lineage*
  • Epithelium / pathology
  • GATA3 Transcription Factor / deficiency
  • GATA3 Transcription Factor / metabolism*
  • Hepatocyte Nuclear Factor 3-alpha / genetics
  • Lactation / physiology
  • Mammary Glands, Animal / cytology*
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / pathology
  • Mice
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic / genetics
  • Time Factors

Substances

  • Foxa1 protein, mouse
  • GATA3 Transcription Factor
  • Hepatocyte Nuclear Factor 3-alpha

Associated data

  • GEO/GSE2988
  • GEO/GSE5602