Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium.
Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium.
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DOI：
10.1083/jcb.200107065
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发表时间：
2001-11-12
影响因子：
7.8
通讯作者：
Hennighausen, L
中科院分区：
文献类型：
--
作者：
Miyoshi, K;Shillingford, J M;Smith, G H;Grimm, S L;Wagner, K U;Oka, T;Rosen, J M;Robinson, G W;Hennighausen, L
怀孕期间乳腺上皮的功能发育取决于催乳素信号传导。然而，潜在的分子和细胞事件尚未完全了解。我们研究了催乳素受体（PrlR）以及转录5a和5b的信号转导子和激活子（称为Stat5）在乳腺泡上皮形成和分化中的具体贡献。将 PrlR 和 Stat5 缺失的乳腺上皮移植到野生型宿主中，并在组织学和分子水平上研究妊娠介导的发育。 Stat5缺失的乳腺上皮发育出导管，但未能形成肺泡，并且没有观察到乳蛋白基因表达。相反，PrlR 无效上皮形成具有小开放管腔的肺泡样结构。电子显微镜揭示了 PrlR 和 Stat5 缺失上皮细胞的未分化特征以及细胞间接触的扰动。 NKCC1（一种导管上皮细胞特有的 Na-K-Cl 协同转运蛋白）和 ZO-1（一种与紧密连接相关的蛋白质）的表达在 PrlR 和 Stat5 缺失上皮细胞的肺泡样结构中得以维持。相比之下，Na-Pi 协同转运蛋白 Npt2b 和间隙连接成分连接蛋白 32（通常在分泌性上皮细胞中表达）在 PrlR 和 Stat5 缺失小鼠中检测不到。这些数据表明，通过 PrlR 和 Stat5 发出的信号对于妊娠期间乳腺肺泡的增殖和分化至关重要。
Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined the specific contributions of the prolactin receptor (PrlR) and the signal transducers and activators of transcription 5a and 5b (referred to as Stat5) in the formation and differentiation of mammary alveolar epithelium. PrlR- and Stat5-null mammary epithelia were transplanted into wild-type hosts, and pregnancy-mediated development was investigated at a histological and molecular level. Stat5-null mammary epithelium developed ducts but failed to form alveoli, and no milk protein gene expression was observed. In contrast, PrlR-null epithelium formed alveoli-like structures with small open lumina. Electron microscopy revealed undifferentiated features of organelles and a perturbation of cell–cell contacts in PrlR- and Stat5-null epithelia. Expression of NKCC1, an Na-K-Cl cotransporter characteristic for ductal epithelia, and ZO-1, a protein associated with tight junction, were maintained in the alveoli-like structures of PrlR- and Stat5-null epithelia. In contrast, the Na-Pi cotransporter Npt2b, and the gap junction component connexin 32, usually expressed in secretory epithelia, were undetectable in PrlR- and Stat5-null mice. These data demonstrate that signaling via the PrlR and Stat5 is critical for the proliferation and differentiation of mammary alveoli during pregnancy.