DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click HERE
to register or log in.
Involvement of the Tyrosine Phosphatase SHP-1 in the Development of Breast Cancer
Final rept. 1 Oct 1998-30 Sep 2002
VIRGINIA UNIV CHARLOTTESVILLE
Pagination or Media Count:
Purpose To test the working hypothesis that SHP-1 is essential for controlling growth and differentiation of mammary epithelial cells and that its dysregulation contributes to the development of breast cancer. Scope To biochemically and functionally characterize SHP-1 in human breast cancer cell lines and to define its biological function in normal epithelial cells. Major Findings We have shown that SHP-1 associates with the EGFR in an EOF stimulation-dependent manner. In addition, we have found that SHP-1 localizes to the lipid rafts. Moreover, our data indicate a functional difference between rafts- and non-rafts-associated fractions of SHP-1. While most of the subcellular localization studies have been performed in hematopoietic cells, in experiments using human breast cancer cells, we have observed that limited amounts of SHP-1 localize to lipid rafts before and after BGF stimulation. In addition, we have obtained additional data showing that a transgenic mouse expressing SHP-1 under its own hematopoietic promoter can partially rescue the motheaten phenotype, which has helped to start the development of a new mouse model. Significance We expect to gain a better understanding of SHP-1s role in epithelial cells and thereby to learn how a dysregulated SHP-1 is potentially involved in the onsetprogression of breast cancer.
APPROVED FOR PUBLIC RELEASE