The aim of this Core facility is to provide murine and human pathology services by experienced pathologists combining uniquely an extensive background expertise in the pathology and molecular analysis of human and mouse development and oncogenesis. All four projects of the proposed Program involve the study of the consequences of mutations introduced into mice either transgenic or by gene targeting technology, or as xenografts from genetically modified human breast cancer cell lines. Moreover, the expression of candidate genes and distribution of their gene products need to be surveyed as they relate to human basal-like breast cancer (BBC). These studies require expert and efficient pathological analyses of large numbers of specimens (tumors and other mouse tissues possibley affected by metastases, xenografts, on occasion, embryos, and tissue microarrays (TMAs) of human breast cancer) to investigate tumorigenesis and/or phenotypic manifestations affecting murine development and translate the significance of such findings to human BBC. The diagnostic procedures that are central to the implementation of the experimental plans and the progress of the Program include macroscopic anatomic examination, microscopic histology, immunohistochemistry and quantitative rtPCR. The Core Leader has provided such services for the last five years in the function of Co-Leader of the Mouse Pathology facility under the auspices of previous support by the NCI. Accordingly, his experience provides assurance for optimal operation of this Core. In fact, quality control is completely secured, as the procedures that are involved have already been optimized, standardized and streamlined. It is projected, therefore, that interpretations will be provided rapidly and efficiently. Moreover, the previous experience guarantees active interactions with the Program participants enhancing the development of projects involving mouse models, in-vitro studies of cell lines and xenografts. Dr. Hanina Hibshoosh an expert human breast cancer pathologist will join the core to provide professional pathology services with the focus on analysis of preferential expression and distribution of candidate genes identified by the Program in human BBCs.
Core B will conduct the histopathological analysis for all four projects of this Program with a projected use of approximately 25% per project. Core B will also perform translational studies of all canditate oncoproteins and tumor suppressors indicated by the Program to detemine their relevance for human basal-like breast cancer.
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