GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland.
Cell, 2006/12/01;127(5):1041-55.
Kouros-Mehr H[1], Slorach EM, Sternlicht MD, Werb Z
Affiliations
PMID: 17129787
Impact factor: 66.85
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.
MeSH terms
Animals; Cell Death; Cell Differentiation; Cell Lineage; Epithelium; GATA3 Transcription Factor; Hepatocyte Nuclear Factor 3-alpha; Lactation; Mammary Glands, Animal; Mice; Mice, Inbred C57BL; Promoter Regions, Genetic; Time Factors
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download