The Role of PTHrP in Epithelial Stromal Interactions During Breast Development.

Recent studies from our laboratory have demonstrated that PTHrP is essential for mammary gland development. The current project was designed to explore the hypothesis that PTHrP is an important contributor to epithelial-mesenchymal interactions that are necessary for mammary development. In the first year, we concentrated on defining the temporal-spatial pattern of PTHrP and PTHPTHrP receptor expression during mammary development. We have learned that during ductal morphogenesis, PTHrP is expressed in mammary epithelial cells and its receptor is expressed in surrounding mesenchymal cells. In addition, it appears that in the post-natal mammary gland, expression of the PTHrP and the PTHPTHrP receptor genes is most intense in terminal end buds, regions of active proliferation and ductal morphogenesis during puberty. The results from these experiments suggest that PTHrP, produced by mammary epithelial cells, acts on mammary stromal cells and modulates their function. We haye generated primary cultures of mouse mammary stromal cells that bind to PTllrP with high a and respond to PTHrP with an increase in cAMP. In years two and three, we will use this experimental system to examine the effects of PTHrP on mammary stromal cell function and how these effects impact the proliferation and morphogenesis of mammary epithelial cells.