GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland
GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland
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DOI：
10.1016/j.cell.2006.09.048
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发表时间：
2006-12-01
期刊：
影响因子：
64.5
通讯作者：
Werb, Zena
中科院分区：
文献类型：
--
作者：
Kouros-Mehr, Hosein;Slorach, Euan M.;Werb, Zena
加塔家族的转录因子在细胞命运的规范中起着重要的作用。然而，目前尚不清楚这些基因是否是维持发育后细胞分化所必需的。我们确定加塔-3作为最高度富集的转录因子在青春期小鼠的乳腺上皮细胞。加塔-3在乳腺导管的腔细胞和末端芽的体细胞中有表达。在条件性缺失加塔-3后，由于青春期TEB形成失败，小鼠表现出严重的乳房发育缺陷。急性加塔-3丢失后，成年小鼠表现出未分化的管腔细胞扩张，基底膜脱离，这导致长期的半胱天冬酶介导的细胞死亡。此外，FOXA 1被鉴定为乳腺中加塔-3的下游靶标。这表明，加塔-3积极维持腔上皮分化的成年乳腺，这提出了重要的意义，乳腺癌的发病机制。
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.