Abstract:
: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 profile and hormonal regulation. Herein, we define 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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Satoh K,Hovey RC,Malewski T,Warri A,Goldhar AS,Ginsburg E,Saito K,Lydon JP,Vonderhaar BKdoi
10.1038/sj.onc.1210555subject
Has Abstractpub_date
2007-11-29 00:00:00pages
7526-34issue
54eissn
0950-9232issn
1476-5594pii
1210555journal_volume
26pub_type
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