Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2
Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2
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DOI：
10.1038/sj.onc.1210555
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发表时间：
2007-11-29
期刊：
影响因子：
8
通讯作者：
Vonderhaar, B. K.
中科院分区：
文献类型：
--
作者：
Satoh, K.;Hovey, R. C.;Vonderhaar, B. K.
在青春期小鼠乳腺内的分支形态发生是由孕酮（P）指导的。一个含有同源框的转录因子，Msx 2，在分支形态发生的作用，建议从其个体发育的表达pro。le和激素调节。在这里，我们。新的Msx 2表达的时空控制，其表达的调节P和其在导管分支形态发生的直接作用。在体内和体外雌激素（E）存在的情况下，P诱导Msx 2，而在P受体（PR）不存在的情况下，Msx 2表达降低。PR稳定转染到小鼠乳腺上皮细胞中增加了Msx 2的内源性表达及其在体外进行分支形态发生的能力。此外，正常乳腺细胞稳定转染Msx 2表现出增加的分支形态发生在体外，而转基因小鼠表达Msx 2在其乳腺表现出增强的横向分支在早期发展。P对分支形态发生的作用似乎涉及Bmp 2/4。总之，这些数据表明，P，通过PR-A和Bmp 2/4途径，诱导Msx 2，以提高乳腺导管分支。
Branching morphogenesis within the peripubertal mouse mammary gland is directed by progesterone (P). A role for the homeobox-containing transcription factor, Msx2, during branching morphogenesis is suggested from its ontogenic expression pro. le and hormonal regulation. Herein, we de. ne the spatio-temporal control of Msx2 expression, the regulation of its expression by P and its direct role in ductal branching morphogenesis. P induces Msx2 in the presence of estrogen (E) both in vitro and in vivo while absence of the P receptor (PR) decreased Msx2 expression. Stable transfection of PR into mouse mammary epithelial cells increased the endogenous expression of Msx2 and their ability to undergo branching morphogenesis in vitro. Furthermore, normal mammary cells stably-transfected with Msx2 demonstrated increased branching morphogenesis in vitro while transgenic mice expressing Msx2 in their mammary glands demonstrated enhanced lateral branching during early development. The action of P on branching morphogenesis appears to involve Bmp2/4. Together, these data demonstrate that P, acting through PR-A and the Bmp2/4 pathway, induces Msx2 to enhance ductal branching in the mammary glands.