Accession Number : ADA336685

Title :   The Role of PTHrP in Mammary Gland Development and Tumorigenesis.

Descriptive Note : Annual rept. 1 Sep 96-31 Aug 97,

Corporate Author : YALE UNIV NEW HAVEN CT

Personal Author(s) : Wysolmerski, John

PDF Url : ADA336685

Report Date : SEP 1997

Pagination or Media Count : 89

Abstract : PTHrP was originally discovered as the tumor product responsible for the paraneoplastic syndrome of humoral hypercalcemia of malignancy. Recent experiments have shown that PTHrP has an important role as a developmental regulatory molecule. This project is designed to explore the hypothesis that PTHrP is a locally produced growth inhibitor that helps to regulate mammary development. In the first year we concentrated on exploring the consequences of the disruption of the PTHrP gene on mammary development. We found that PTHrP was necessary for embryonic mammary development. In the absence of PTHrP, the embryonic mammary gland failed to initiate branching morphogenesis and the mammary epithelial cells degenerated. We found that these effects were due to the actions of amino-terminal PTHrP acting via the PTH/PTHrP receptor. Furthermore, it appears that PTHrP is produced by the mammary epithelial cells and the PTH/PTHrP receptor is expressed on mammary stromal cells. Therefore our findings suggest that PTHrP serves as a critical signal from the embryonic epithelium to the embryonic mesenchyme in order to allow the mesenchyme to support further development and morphogenesis of the epithelium.

Descriptors :   *MAMMARY GLANDS, *BREAST CANCER, EPITHELIUM, CLINICAL MEDICINE, NEOPLASMS, SIGNALS, GENES, HYPOTHESES, INHIBITORS, MEDICAL SERVICES, EMBRYOS, PREGNANCY, CELLS(BIOLOGY), RIBONUCLEIC ACIDS, RECEPTOR SITES(PHYSIOLOGY), AMINO ACIDS, GROWTH(PHYSIOLOGY), MORPHOGENESIS, PARATHYROID HORMONES, HYPERCAPNIA.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE