GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland
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.
Footnotes
Accession Numbers Microarray data were submitted to the NCBI Gene Expression Omnibus under the accession numbers {"type":"entrez-geo","attrs":{"text":"GSE2988","term_id":"2988"}}GSE2988 and {"type":"entrez-geo","attrs":{"text":"GSE5602","term_id":"5602"}}GSE5602.