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Development of breast cancer is a multistep process involving a complex interplay of both inherited and acquired genetic alterations. In this grant, we have proposed to pursue several lines of studies to define the role of the met tyrosine kinase in the development of breast cancer. First we plan to characterize the structural and functional alterations of the met gene and its product(s) in breast cancers. Second we wish to define the molecular basis of altered met expression in the pathogenesis of mammary epithelial neoplasia. Third we plan to assess the biological consequences of altered met expression with respect to the development and oncogenesis of breast tissues in animal model systems. In this progress report, we have evidence that c-met expression is altered in human breast cancer lines and that activated met oncogene can induce breast cancer development in transgenic mouse model.