Ron in Breast Development and Cancer
Annual summary rept. 21 Oct 2004-30 Sep 2005
CINCINNATI UNIV OH
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Activated growth factor receptor tyrosine kinases have been shown to play pivitotal roles in a variety of human cancers. In this report, our laboratory provides a direct demonstration that Ron receptor overexpression is sufficient to induce mammary transformation and is associated with a high degree of metastasis in a murine model of human breast cancer. These results are in agreement with human cancer studies documenting an upregulation of this receptor in breast tumors as well as are consistent with the correlation between Ron overexpression and an aggressive phenotype observed in node-negative breast tumors1-3. These experiments, therefore, provide a new target for therapeutic intervention of human breast cancer. The purpose of this proposal is to determine the contribution of Ron signaling in normal mammary gland growth and development Aim 1. This is being accomplished by contrasting breast development in wild-type mice compared to mice with a block in Ron signaling. Secondly, the impact of Ron signaling in the pathogenesis of oncogene-driven mammary gland tumors is being evaluated Aim 2. This will be accomplished by monitoring tumor kinetics and downstream signaling cascades in a polyoma virus middle T antigen pMT-induced model of breast carcinogenesis. During the past funding cycle, studies were focused primarily on Aim 2.
- Medicine and Medical Research