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 second year of support include (1) BCAR3 protein expression is elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and DCIS compared to IDC. (2) BCAR3 is significantly upregulated in triple negative breast cancer and normal tissue; (3) BCAR3 expression shows a modest correlation to responsiveness to dasatinib in 2D culture; (4) BCAR3 expression regulates breast tumor initiation and growth in an MDA-MB-231 orthotopic tumor model; and (5) BCAR3 is required for mammary epithelial cells to activate appropriate growth factor signaling pathways that regulate mammary organoid development in 3D cultures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2017
- Accession Number
- AD1050799
Entities
People
- Amy H. Bouton