Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation

Nat Cell Biol. 2007 Feb;9(2):201-9. doi: 10.1038/ncb1530. Epub 2006 Dec 24.


The transcription factor Gata-3 is a defining marker of the 'luminal' subtypes of breast cancer. To gain insight into the role of Gata-3 in breast epithelial development and oncogenesis, we have explored its normal function within the mammary gland by conditionally deleting Gata-3 at different stages of development. We report that Gata-3 has essential roles in the morphogenesis of the mammary gland in both the embryo and adult. Through the discovery of a novel marker (beta3-integrin) of luminal progenitor cells and their purification, we demonstrate that Gata-3 deficiency leads to an expansion of luminal progenitors and a concomitant block in differentiation. Remarkably, introduction of Gata-3 into a stem cell-enriched population induced maturation along the alveolar luminal lineage. These studies provide evidence for the existence of an epithelial hierarchy within the mammary gland and establish Gata-3 as a critical regulator of luminal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • GATA3 Transcription Factor / deficiency
  • GATA3 Transcription Factor / metabolism*
  • GATA3 Transcription Factor / pharmacology
  • Integrin beta3 / biosynthesis
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism*
  • Mice
  • Morphogenesis / drug effects*
  • Pregnancy
  • Stem Cells / metabolism


  • GATA3 Transcription Factor
  • Integrin beta3