The NCI Mammary Collective represents an integrated effort by 25 intramural investigators focused on the development and analysis of mouse models of mammary cancer. Our goals are to compare transgenic murine models of mammary cancer with their human counterparts; to develop a comprehensive database of expression profiles, cytogenetics abnormalities, and descriptive pathology in both mouse and human cancers; to define the most appropriate mammary compartment for targeted expression of selected oncogenes; and to develop new murine models of mammary cancer. Our collective establishes five technology groups which will interrogate these mouse models including mouse model development, microarray gene expression profiling, advanced spectral karyotype analyses, a histopathologic, and molecular pathologic techniques coupled with laser capture microdissection. The data generated in these experiments will be processed through an advanced bioinformatics system to determine which models share important molecular and morphologic signatures with human breast cancer. An outcome of this approach will be the identification of the best targeting vectors for expressing heterologous genes to the correct mammary epithelial cellular compartment. Other experimental approaches will include the development of a novel avian leukemia viral system to introduce multiple genetic alterations into the mammary epithelium in order to study gene-gene interactions in mammary oncogenesis, and the discovery of new applications of the cre-lox system for tissue-specific and temporal regulation of gene expression. The NCI Collective will be a partner with other consortial members in sharing information and reagents to advance the field of modeling human cancer in mouse transgenic systems.