Predicting Sensitivity of Breast Tumors to Src-Targeted Therapies through Assessment of Cas/Src/BCAR3 Activity
Abstract
Purpose: The purpose of this research is to assess the role of a signaling pathway comprised of the protein tyrosine kinase c-Src (Src) and two adaptor molecules, Cas and BCAR3, in promoting breast tumor growth, metastasis and therapeutic resistance toward Src-targeted small molecule inhibitors. Scope: The proposed research employs 2- and 3-dimensional tissue culture models, transplantable mouse models of breast cancer, and analysis of human breast tumor samples. Major Findings: Key results from the third year of support include (1) Further documentation using orthotopic tumor models demonstrating that BCAR3 is essential for tumor growth but that its interaction with Cas appears not to be required for this process; (2) the development of a robust clonigenic assay that we have used to show that BCAR3 controls cell proliferation/survival and dasatinib sensitivity; and(3) the acquisition of RNA-seq data that allow us to compare gene expression profiles as a function ofBCAR3 expression under 3 culture conditions (plastic, 3D matrigel, and murine organoid cultures). The data we have generated are currently being prepared for publication; we expect to submit the manuscript by the end of the year.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1093162
Entities
People
- Amy H. Bouton