Parathyroid Hormone-Related Protein Specifies the Mammary Mesenchyme and Regulates Embryonic Mammary Development

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Abstract

Parathyroid Hormone related Protein (PTHrP) is a critical regulator of mammary gland morphogenesis in the mouse embryo. Loss of PTHrP, or its receptor, PTHR1, results in arrested mammary buds at day 15 of embryonic development (E15). In contrast, overexpression of PTHrP converts the ventral epidermis into hairless nipple skin. PTHrP signaling appears to be critical for mammary mesenchyme specification, which in turn maintains mammary epithelial identity, directs bud outgrowth, disrupts the male mammary rudiment and specifies the formation of the nipple. In the embryonic mammary bud, PTHrP exerts its effects on morphogenesis, in part, through epithelial-stromal crosstalk mediated by Wnt and BMP signaling. Recently, PTHLH has been identified as a strong candidate for a novel breast cancer susceptibility locus, although PTHrP’s role in breast cancer has not been clearly defined. The effects of PTHrP on the growth of the embryonic mammary rudiment and its invasion into the dermis may, in turn, have connections to the role of PTHrP in breast cancer.

Keywords

PTHrP Mammary Development Embryonic Breast Wnt Bmp 

Abbreviations

PTHrP

Parathyroid hormone related protein

K14

Keratin 14

PTHR1

Parathyroid hormone receptor, type I

WT

Wild-type

AR

Androgen receptor

ER

Estrogen receptor

BMP

Bone morphogenic protein

MMP

Matrix metalloprotease

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Notes

Acknowledgments

JW is supported by National Institutes of Health (NIH) grants R01 DK55501, R01 CA153702 and R01 DK077565. MH is supported by the Idaho INBRE Program [P20 RR016454 and P20GM103408] and by a postdoctoral fellowship from the Department of Defense Breast Cancer Research program (W81XWH-09-1-0580). We would like to thank Dr. Kata Granic for providing images of PTHrP-lacZ embryos.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.S-128 Department of Biological SciencesBoise State UniversityBoiseUSA
  2. 2.Department of Internal MedicineYale University School of MedicineNew HavenUSA

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