Parathyroid hormone-related protein is not required for normal ductal or alveolar development in the post-natal mammary gland.
Parathyroid hormone-related protein is not required for normal ductal or alveolar development in the post-natal mammary gland.
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DOI：
10.1371/journal.pone.0027278
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wysolmerski J
中科院分区：
文献类型：
--
作者：
Boras-Granic K;VanHouten J;Hiremath M;Wysolmerski J
PTHrP是胚胎乳腺形成所必需的，如果没有PTHrP，胚胎乳房芽就不能形成新生儿导管系统。此外，PTHrP是在哺乳期间由乳房产生的，在乳汁生产过程中有助于调节母亲的钙稳态。在这项研究中，我们研究了甲状旁腺素受体在出生后乳房发育中的作用。利用PTHrP-LacZ转基因小鼠，观察了PTHrP基因在小鼠乳腺发育过程中的表达。我们发现，PTHrP在青春期发育期间仅在腺体的基底细胞中表达，在妊娠和哺乳期的乳汁分泌肺泡细胞中表达。根据先前发现PTHrP在帽细胞和肌上皮细胞中的过表达抑制了青春期导管的延长，我们预测去除出生后腺体中天然的PTHrP表达将导致导管的加速发育。为了解决这一假设，我们生成了两个针对出生后乳腺的PTHrP缺乏症条件模型。我们使用MMTV-Cre转基因来阻断腔上皮细胞和肌上皮细胞中的PTHrP基因，并使用四环素调节的K14-TTA；Teto-Cre转基因来靶向PTHrP在肌上皮细胞和CAP细胞中的表达。在两种PTHrP消融模型中，我们发现尽管没有PTHrP，乳房发育仍正常进行。我们得出结论，PTHrP信号不是正常的导管或肺泡发育所必需的。
PTHrP is necessary for the formation of the embryonic mammary gland and, in its absence, the embryonic mammary bud fails to form the neonatal duct system. In addition, PTHrP is produced by the breast during lactation and contributes to the regulation of maternal calcium homeostasis during milk production. In this study, we examined the role of PTHrP during post-natal mammary development. Using a PTHrP-lacZ transgenic mouse, we surveyed the expression of PTHrP in the developing post-natal mouse mammary gland. We found that PTHrP expression is restricted to the basal cells of the gland during pubertal development and becomes expressed in milk secreting alveolar cells during pregnancy and lactation. Based on the previous findings that overexpression of PTHrP in cap and myoepithelial cells inhibited ductal elongation during puberty, we predicted that ablation of native PTHrP expression in the post-natal gland would result in accelerated ductal development. To address this hypothesis, we generated two conditional models of PTHrP-deficiency specifically targeted to the postnatal mammary gland. We used the MMTV-Cre transgene to ablate the floxed PTHrP gene in both luminal and myoepithelial cells and a tetracycline-regulated K14-tTA;tetO-Cre transgene to target PTHrP expression in just myoepithelial and cap cells. In both models of PTHrP ablation, we found that mammary development proceeds normally despite the absence of PTHrP. We conclude that PTHrP signaling is not required for normal ductal or alveolar development.
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影响因子：
4.6
作者：
Dewar, Rajan;Fadare, Oluwole;Gown, Allen M.
通讯作者：
Gown, Allen M.
影响因子：
64.5
作者：
Kouros-Mehr, Hosein;Slorach, Euan M.;Werb, Zena
通讯作者：
Werb, Zena
影响因子：
3
作者：
Wagner, KU;McAllister, K;Hennighausen, L
通讯作者：
Hennighausen, L
DOI：
10.1186/bcr1368
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Sternlicht MD
通讯作者：
Sternlicht MD
影响因子：
2.9
作者：
Sternlicht, Mark D.;Kouros-Mehr, Hosein;Werb, Zena
通讯作者：
Werb, Zena