The Role of PTHrP in Mammary Gland Development and Tumorigenesis
Annual rept. 1 Sep 1998-31 Aug 1999
YALE UNIV NEW HAVEN CT
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PTHrP was discovered as the tumor product responsible for the syndrome of humoral hypercalcemia of malignancy. Experiments in the first two years of this project have shown that PTHrP has an important role during embryonic mammary development. In the third year of this project we have gained a deeper understanding of PTHrPs functions in the embryonic development of the mammary gland. PTHrP is expressed within epithelial cells, during the early stages of mammary bud formation. The PTHrP receptor is expressed throughout the sub-epidermal mesenchyme. In those mesenchymal cells closest to the mammary epithelial bud, PTHrP induces a change in cell fate allowing those cells to become functional mammary mesenchymal cells. If PTHrP is absent, these cells differentiate into dermal cells that are incapable of supporting further epithelial development, and the expected morphogenesis of the mammary gland fails to occur. In addition, we have demonstrated that transient overexpression of PTHrP during embryonic development of the mammary gland has profound consequences for the branching pattern produced by the mammary epithelial ducts during adolescent development. This again underscores the fact that, during the embryonic formation of the mammary gland, PTHrP exerts powerful effects on mammary morphogenesis. Finally, we have begun to study the effects of PTHrP overexpression on D MBA-induced mammary tumorigenesis in mice.
- Anatomy and Physiology
- Medicine and Medical Research