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Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2

Oncogene volume 26, pages 7526–7534 (2007)Cite this article

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.

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Acknowledgements

We thank Dr Lionel Fiegenbaum of the NCI Frederick Cancer Research and Development Center for helping generate the MMTV-Msx2 transgenic mice. This research was supported by the Intramural Research Program of the NIH, Center for Cancer Research, NCI.

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Author notes

  1. K Satoh

    Present address: 3Current address: Division of Gastroenterology, Tohoku University, Graduate School of Medicine, 1-1, Seiryo-machi, Aobaku, Sendai 980-8574, Japan.,

  2. R C Hovey

    Present address: 4Current address: Department of Animal Science, University of Vermont, Burlington, VT, USA.,

  3. T Malewski

    Present address: 5Current address: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Jastrzebiec, Poland.,

  4. A Warri

    Present address: 6Current address: University of Turku, Turku, Finland.,

Authors and Affiliations

  1. Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    K Satoh, R C Hovey, T Malewski, A Warri, A S Goldhar, E Ginsburg, K Saito & B K Vonderhaar

  2. Department of Cell Biology, Baylor College of Medicine, Houston, TX, USA

    J P Lydon

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Correspondence to B K Vonderhaar.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Satoh, K., Hovey, R., Malewski, T. et al. Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2. Oncogene 26, 7526–7534 (2007). https://doi.org/10.1038/sj.onc.1210555

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