Ron in Breast Development and Cancer
Annual summary 1 Oct 2005-30 Sep 2006
CINCINNATI UNIV OH
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The objective of this project is to define the in vivo role of the receptor tyrosine kinase Ron in mammary gland biology. Virtually nothing is known regarding the function of Ron in the breast. However, two recent studies have shown that Ron is over-expressed and highly phosphorylated in a significant fraction of human and feline breast cancers. To define the in vivo significance of Ron, mice were generated with a targeted ablation of the tyrosine kinase domain of this receptor TK4- mice. To determine the impact of Ron in a murine model of breast cancer, the TK4- mice were crossed to mice expressing the polyoma virus middle T antigen pMT under control of the mouse mammary tumor virus promoter. Both TK4- and control mice expressing pMT develop mammary tumors and lung metastasis. However, a significant decrease in mammary tumor initiation and growth was found in the TK4- mice compared to controls. This decrease was associated with a significant decrease in microvessel density, decreased cellular proliferation and increased apoptosis. Biochemical analyses showed that the pMT expressing TK4- tumors had defects in MAPK and AKT activation. Our studies are the first to demonstrate the impact of Ron signaling on tumorigenesis.
- Anatomy and Physiology
- Medicine and Medical Research