Overexpression of parathyroid hormone-related protein or parathyroid hormone in transgenic mice impairs branching morphogenesis during mammary gland development.
Overexpression of parathyroid hormone-related protein or parathyroid hormone in transgenic mice impairs branching morphogenesis during mammary gland development.
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DOI：
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发表时间：
1995-11
期刊：
影响因子：
4.6
通讯作者：
J. Wysolmerski;James F. McCaughern-Carucci;A. Daifotis;A. Broadus;W. Philbrick
中科院分区：
文献类型：
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作者：
J. Wysolmerski;James F. McCaughern-Carucci;A. Daifotis;A. Broadus;W. Philbrick
甲状旁腺相关蛋白（PTHrP）最初是作为引起恶性肿瘤体液性高钙血症的肿瘤产物而被发现的。PTHrP广泛表达于许多正常胎儿组织中，参与器官发生的调控。在这份报告中，我们的文件，PTHrP在转基因小鼠的乳腺肌上皮细胞中的过度表达导致了一种形式的乳房发育不全，其特征在于一个深刻的缺陷，在分支发育中的乳腺导管系统的形态发生。此外，转基因小鼠在妊娠期间表现出小叶肺泡发育缺陷，这似乎部分是由于雌激素和孕激素刺激后形成终末导管的能力受损所致。PTHrP对乳腺发育过程中分支形态发生的影响似乎是通过PTH/PTHrP受体发出信号的氨基末端PTH样序列的结果，因为转基因小鼠乳腺中甲状旁腺激素本身的过度表达引起了类似的发育表型，并且通过局部植入缓释颗粒递送PTHrP（1-36）损害了正常小鼠的乳腺发育。这些结果表明，PTHrP，这是一个天然产物的乳腺上皮细胞和肌上皮细胞可能参与正常的乳房发育，可能作为一个局部分泌的生长抑制剂。
Parathyroid hormone-related protein (PTHrP) was originally discovered as the tumor product that causes humoral hypercalcemia of malignancy. PTHrP is now known to be widely expressed in many normal fetal tissues where it may participate in the regulation of organogenesis. In this report, we document that overexpression of PTHrP in myoepithelial cells in the mammary glands of transgenic mice resulted in a form of breast hypoplasia characterized by a profound defect in branching morphogenesis of the developing mammary duct system. In addition, transgenic mice manifested a defect in lobuloalveolar development during pregnancy that seemed to be, in part, the consequence of an impaired ability to form terminal ducts in response to estrogen and progesterone stimulation. The effects of PTHrP on branching morphogenesis during breast development appeared to be the result of amino-terminal PTH-like sequences that signal through the PTH/PTHrP receptor, since overexpression of parathyroid hormone itself in the mammary glands of transgenic mice caused a similar development phenotype, and delivery of PTHrP (1-36) via locally implanted slow-release pellets impaired breast development in normal mice. These results suggest that PTHrP, which is a native product of mammary epithelial and myoepithelial cells may participate in normal breast development, perhaps as a locally secreted growth inhibitor.