The Role of PTHrP in Mammary Gland Development and Tumorigenesis
Abstract
PTHrP was discovered as The tumor product responsible for the syndrome of humoral hypercalcemia of malignancy. It is know known to be an important developmental regulatory molecule in several sites, including the mammary gland. Over the four years of this grant, we have used a variety of animal models to investigate the functions of PTHrP during mammary development. We have discovered that PTHrP is necessary for mammary gland formation in the embryo. Our data suggest that PTHrP signaling is involved regulating an intricate series of cell fate decisions that govern the proper differentiation of the mammary epithelium and mammary mesenchyme as well as the proper morphogenesis of the mammary ducts and nipple. We have also studied the effects of PTHrP overexpression during the pubertal development of the mammary gland. Here, it appears that PTHrP regulates epithelial cell proliferation and apoptosis within terminal endbuds, and antagonizes the effects of estrogen and progesterone on these processes. Finally, overexpression of PTHrP appears to increase the incidence and shorten the latency of mammary tumor formation when mice are treated with a chemical carcinogen.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA391907
Entities
People
- John J. Wysolmerski
Organizations
- Yale University