Breast cancer is the most common cancer among women in the United States and results in over 42,000 deaths annually. Although breast cancer appears most frequently in women over 40 years of age, it is the result of multiple molecular alterations, the first of which occurs in teenage years. The mouse mammary tumor system is a classic example of multiple stage tumorigenesis. It is the long term objectives of this research program to detect and analyze the molecular alterations associated with the early stages of mammary tumorigenesis. Three experimental strategies are proposed to achieve these goals. A gene expression screen utilizing polymerase chain reaction methodologies will be used to identify unique genes associated with preneoplastic hyperplasia and tumorigenic potential. Secondly, the expression of the unique genes as well as genes wnt5A, wnt5B and bcl-l will be examined by RNA Northern and slot blots in order to assess the significance and role of these genes in mammary preneoplastic and neoplastic transformation. When feasible, protein expression will be evaluated by immuno-histochemical procedures. Finally, the ability of specific genes to alter the tumorigenic process will be assessed by transfection methods into mammary epithelial cells in vitro and analyzed by growth patterns in vivo and in vitro. The results should identify specific genes associated with the early stages of mammary epithelial cell transformation.
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