Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation
Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation
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DOI：
10.1038/ncb1530
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发表时间：
2007-02-01
影响因子：
21.3
通讯作者：
Visvader, Jane E.
中科院分区：
文献类型：
--
作者：
Asselin-Labat, Marie-Liesse;Sutherland, Kate D.;Visvader, Jane E.
转录因子加塔-3是乳腺癌“管腔”亚型的定义标志物（1-4）。为了深入了解加塔-3在乳腺上皮发育和肿瘤发生中的作用，我们通过在不同发育阶段条件性缺失加塔-3来探索其在乳腺内的正常功能。我们报告说，加塔-3在胚胎和成人乳腺的形态发生中具有重要作用。通过发现管腔祖细胞的新标记物（β（3）-整联蛋白）及其纯化，我们证明了加塔-3缺乏导致管腔祖细胞的扩增和伴随的分化阻滞。值得注意的是，将加塔-3引入富含干细胞的群体中可诱导肺泡腔谱系沿着成熟。这些研究为乳腺内存在上皮层级提供了证据，并确立了加塔-3作为管腔分化的关键调节剂。
The transcription factor Gata-3 is a defining marker of the 'luminal' subtypes of breast cancer(1-4). To gain insight into the role of Gata-3 in breast epithelial development and oncogenesis, we have explored its normal function within the mammary gland by conditionally deleting Gata-3 at different stages of development. We report that Gata-3 has essential roles in the morphogenesis of the mammary gland in both the embryo and adult. Through the discovery of a novel marker (beta(3)-integrin) of luminal progenitor cells and their purification, we demonstrate that Gata-3 deficiency leads to an expansion of luminal progenitors and a concomitant block in differentiation. Remarkably, introduction of Gata-3 into a stem cell-enriched population induced maturation along the alveolar luminal lineage. These studies provide evidence for the existence of an epithelial hierarchy within the mammary gland and establish Gata-3 as a critical regulator of luminal differentiation.