Murine Models of Breast Cancer: Assessment of the Role of c-Scr in Mammary Tumorigenesis
Abstract
Strong evidence exists that the c-Src non-receptor tyrosine kinase plays a role in the pathology of human breast tumors. The purpose of this study is to examine the role of c- Src in mammary tumorigenesis and elucidate the mechanisms that lead to tumor formation in an animal model for breast cancer. In our previous experiments, we used Src substrates that we cloned to activate c-Src and study its signaling mechanisms. Using one of these substrates, Sin, we characterized a signaling cascade that is activated as a result of Sin binding to Src and Src-mediated Sin phosphorylation, and involves activation of the small GTP-binding protein Rap1. More recently we found that Sin, when phosphorylated by Src kinases, forms a signaling complex consisting of signaling intermediates including the Src related tyrosine kinase Fyn and phospholypase C-gamma (PLC-7). We also found that Sin regulates cell signaling by controlling the activation of PLC-gamma, which is important for proliferation in many different cell types. In future experiments, we will use inhibitory RNA oligonucleotides to address the effect of lack of Sin on cellular growth and transformation and we will isolate the Sin protein complex from breast cancer cell lines. These experiments will provide insight into the mechanisms of Src kinase/Sin-mediated tumorigenesis and may lead to the identification of proteins that will be used as targets for drug development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA421769
Entities
People
- Konstantina Alexandropoulos
Organizations
- Columbia University