Ron in Breast Development and Cancer
Abstract
The long-term 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 (TK-/- mice). To determine the impact of Ron in a murine model of breast cancer, the TK-/- mice were crossed to mice expressing the polyoma virus middle T antigen (pMT) under control of the mouse mammary tumor virus promoter. Both TK-/- 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 TK-/- 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 TK-/- tumors had defects in MAPK and AKT activation. Our studies are the first to demonstrate the impact of Ron signaling on tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA436414
Entities
People
- Susan E. Waltz
Organizations
- University of Cincinnati