期刊
CELL
卷 127, 期 5, 页码 1041-1055出版社
CELL PRESS
DOI: 10.1016/j.cell.2006.09.048
关键词
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资金
- NCI NIH HHS [R01 CA057621, R01 CA057621-16A1, R01 CA057621-15, CA057621] Funding Source: Medline
- NIEHS NIH HHS [ES012801, U01 ES012801, U01 ES012801-04S3] Funding Source: Medline
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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