[HTML][HTML] GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland

H Kouros-Mehr, EM Slorach, MD Sternlicht, Z Werb - Cell, 2006 - cell.com
H Kouros-Mehr, EM Slorach, MD Sternlicht, Z Werb
Cell, 2006cell.com
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 …
Summary
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.
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