Perturbation of β1-integrin mammary gland results in function in involuting premature dedifferentiation of secretory epithelial cells
Perturbation of β1-integrin mammary gland results in function in involuting premature dedifferentiation of secretory epithelial cells
复制标题
DOI：
10.1091/mbc.e02-02-0086
复制
发表时间：
2002-10-01
影响因子：
3.3
通讯作者：
Glukhova, MA
中科院分区：
文献类型：
--
作者：
Faraldo, MM;Deugnier, MA;Glukhova, MA
为了研究β -整合素在体内的作用机制，我们在小鼠乳腺肿瘤病毒（MMTV）启动子（MMTV- β -cyto）的控制下，构建了表达β -整合素显性负突变体的转基因小鼠。mmtv - β -cyto转基因雌性乳腺在妊娠和哺乳期表现出明显的生长缺陷，泌乳初期分泌上皮细胞分化受损。我们在本文中报道了β -整合素功能的扰动诱导了内分泌上皮的过早去分化，表现为β -酪蛋白和乳清酸性蛋白mRNA水平的过早下降，伴随着STAT5（乳腺发育所必需的转录因子）的失活和STAT5信号负调节因子核因子- κ b （STAT5信号的负调节因子）的上调。这是第一个在体内证明包括β -整合素在内的细胞外基质相互作用在控制乳基因转录和维持乳腺上皮细胞分化状态中发挥重要作用的研究。
To study the mechanism of beta1-integrin function in vivo, we have generated transgenic mouse expressing a dominant negative mutant of beta1-integrin under the control of mouse mammary tumor virus (MMTV) promoter (MMTV-beta1-cyto). Mammary glands from MMTV-beta1-cyto transgenic females present significant growth defects during pregnancy and lactation and impaired differentiation of secretory epithelial cells at the onset of lactation. We report herein that perturbation of beta1-integrin function in involuting mammary gland induced precocious dedifferentiation of the secretory epithelium, as shown by the premature decrease in beta-casein and whey acidic protein mRNA levels, accompanied by inactivation of STAT5, a transcription factor essential for mammary gland development and up-regulation of nuclear factor-kappaB, a negative regulator of STAT5 signaling. This is the first study demonstrating in vivo that cell-extracellular matrix interactions involving beta1-integrins play an important role in the control of milk gene transcription and in the maintenance of the mammary epithelial cell differentiated state.