Involvement of the Tyrosine Phosphatase SHP-1 in the Development of Breast Cancer
Final rept. 1 Oct 1998-30 Sep 2002
VIRGINIA UNIV CHARLOTTESVILLE
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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.
- Anatomy and Physiology
- Medicine and Medical Research