The Role of Src Tyrosine Kinase Signaling Networks in the Development and Progression of Ovarian Cancer in a Mouse Model
Abstract
Ovarian cancer is among the most common and deadly malignancies in women, accounting for nearly 15,000 deaths per year in the United States. We have developed a mouse model of ovarian cancer, which will allow for new studies into the biochemical changes that occur in the tumorigenic process. We have determined that Src tyrosine kinase is over expressed and constitutively activated in these mouse ovarian cancer cells. This leads to constitutive activation of downstream kinases such as phosphatidylinositol-3-kinase (PI3-kinase) and focal adhesion kinase (FAK). Pharmacologic inhibition of Src suppresses cell migration, alters localization of FAK, decreases protein tyrosine kinase phosphorylation and enhances the cell killing effects of the taxol, a commonly used chemotherapeutic agent in women with ovarian cancer. We have produced an inducible, epitope tagged Src dominant negative and are currently isolating clonal cell lines for characterization of the effects of Src dominant negative expression. These cells lines will be used for both in vitro and in vivo studies on the role of Src tyrosine kinase and its substrates in the growth of ovarian cancer cells and on the chemotherapeutic sensitivity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA406212
Entities
People
- Christopher C. Taylor
Organizations
- Georgetown University