The primary focus of our laboratory has been the functional characterization of a steroid-driven growth factor, the granulin-epithelin precursor (GEP), in endometrial and ovarian cancer. We hypothesize that GEP plays a role in the survival and metastases of these cancers and we are using siRNA strategies to explore this hypothesis. We are also examining novel mechanisms of GEP regulation through analysis of its promoter. Additional laboratory efforts are driven by the hypothesis that the molecular analysis of select populations of endometrial cancer cells will uncover novel and cell-specific therapeutic targets for this disease. Toward that end, we have coupled the technique of laser capture microdissection with reverse phase protein array analysis to identify signaling pathways important in endometrial cancer progression. Based on our analysis, we have begun in vitro experiments examining the capacity of compounds targeted specifically toward the predominate pathway, to induce apoptosis and inhibit proliferation. In vivo experiments using these compounds will be pre-clinical data for Phase II trials utilizing the most effective compounds identified. Data gained from this work will validate the utility of reverse phase phoshoprotein array analysis from select populations of cells to eventually predict responders and non-responders to molecular therapeutic agents.