MOLECULAR/CELLULAR APPROACHES TO BREAST CANCER DIAGNOSIS

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This program represents a multidiciplinary approach towards developing new diagnostic and prognostic indicators for breast cancer. This approach tests the hypothesis that recent advances in molecular and cellular biology using model systems are ready to be applied directly to the problem of human breast cancer. The research projects will concentrate on three areas; 1) oncogene expression, by comparing normal and malignant breast epithelial cells in short-term culture for expression of known oncogenes and for activation or amplification of potentially new oncogenes; 2) genetic instability, by examining cultured breast cells for loss of heterozygosity using restriction fragment length polymorphism analysis and for their capacity to generate gene amplifications, and 3) stromal-epithelial interactions looking for systemic manifestations of breast cancer by comparing skin and breast- derived fibroblasts from normal donors and breast cancer patients for expression of extracellular matrix components, cell phenotype differences, and stromal interactions with breast epithelial cells. The Program's Clinical Core will provide the projects and the other cores with surgical breast specimens and fine needle aspiration material, will conduct the clinical protocols designed to obtain new prognostic data about tumor cell kinetics, and in association with the Administrative Core will provide clinical data and prospective follow-up information on all patients whose tumor samples are being analyzed. The Cell Biology Core will process and bank benign and malignant breast tissue specimens, producing homogeneous preparations of epithelial and stromal cells which can be propagated and expanded in short-term cultures for use by the research projects. This core, in association with the Cytometry and Biostatics Core, will also routinely characterize all biopsy and fine-needle aspiration material using a panel of monoclonal antibodies and analytical procedures to quantify cellular phenotypic markers and indices of tumor cytokinetics. These molecular and cellular studies will be used to optimize and augment the routine assays being performed on biopsy material. Hopefully, the results from these studies will impact on breast cancer survival by improving our diagnostic and prognostic indicators, as well as by providing new scientific insights into breast cancer pathophysiology.