Cancers arise and progress by a series of genetic and biochemical events that remain to be fully described.During the initial period of support for this project, we have characterized several mouse models of breastcarcinoma by examining morphological features, lymph node dependence, their genotypes and expressionphenotypes, and mechanisms of oncogenesis by Wnt signaling elements. We have also learned to deliverviral vectors to mammary and pancreatic islet cells and have confirmed the ability of two candidate genes topromote tumor progression in islet cells. In the new proposal, we continue to use a variety of mouse modelsof breast cancer and a model of islet cell carcinogenesis, plus three dimensional tissue culture methods andmaterials from stored human tumor samples, to explore several issues related to the molecular basis ofneoplasia. Virus vectors will be used to assess many genes and micro-RNAs as contributors to tumorprogression in the pancreatic and mammary cancer models. We will seek to understand the phenomenonof oncogene dependence by using conditional oncogenic transgenes and viral vectors to identify factors thatprotect tumors from oncogene-dependence. And we will explore our preliminary evidence that oncogenesisby components of Wnt signaling pathways is mediated by fibroblast growth factors or members of the proteinkinase C (PKC) family.
Showing the most recent 10 out of 97 publications