The Role of RPTP-Alpha-Like Protein Tyrosine Phosphatases in Mammary Tumorigenesis

The aim of the studies covered under this report was to start addressing the potential role of protein tyrosine phosphatases in mammary tumorigenesis. On theoretical grounds, this class of enzymes could be expected to either act as negative regulators of growth (e.g. tumor suppressors), or to act oncogenically, e.g. by their ability to activate kinases that are negatively regulated by phosphorylation. We have addressed this question using RPTPa as a model PTP. Expression of this PTP has been surveyed in human breast cancers, in vitro studies have been performed to assess the effect of this PTP on growth properties and tumorigenicity of mammary carcinoma cells. Both approaches have led to the conclusion that increased expression of this PTP correlates with a less advanced stage of tumor progression. A number of studies have also been started to address the effect of RPTPa mouse gene ablation on models of mouse mammary tumorigenesis. These results suggest RPTPa may be useful as a marker for tumor progression, and raise a cautionary note regarding the use of PTP inhibitors in tumor therapy. These studies have been delayed with respect to the original timetable, but are proceeding. ______ Original contains color plates: All DTIC reproductions will be in black and white.