The objectives of this proposal are to identify genes, proteins and molecular pathways involved in regulating the metastasis of breast cancer to specific organs. To achieve these objectives we will use a combination of gene expression profiling, bioinformatic analysis, histology of human female breast cancer samples, genetic manipulation of transplantable tumour cells and transgenic mouse technology. In addition to finding new genes, we aim to analyse to what extent genes already known to play a role in breast cancer metastasis specify which organs breast tumours metastasise to. We will also establish how the currently known genes that are associated with breast cancer dissemination and the new ones we identify fit together into pathways that regulate organ- specific metastasis. These findings will be coupled with the analysis of clinical trials that participants in this consortium are involved in. Further deliverables include the development of improved animal models for the study of breast cancer metastasis, and the development of diagnostic methods for determining whether primary tumours already have metastatic potential. Together, the work packages in this proposal will establish a pipeline of activities that unite basic research into the organ-specific metastasis of breast cancer with target validation and clinical application.
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