Role of Rac GTPasas in Chemokine-Stimulated Breast Carcinoma Metastasis
Abstract
CXCR4 is highly expressed in breast carcinoma cells and is essential for breast cancer metastasis to the lung. CXCR4 is the receptor for CXCL12 a chemokine that is enriched in organs that are targeted by metastatic breast cancer such as lung and liver. The molecular mechanisms of CXCR4-mediated breast cancer metastasis however are poorly understood. In this project we test the hypothesis that Rac proteins are essential for CXCR4-mediated breast carcinoma cell proliferation and survival thereby contributing to breast cancer metastasis. The Rac proteins examined comprise Rac1 Rac1b and Rac3. In Task I we investigate the role of Rac proteins in CXCL12-regulated breast carcinoma cell proliferation and survival in vitro. In Task 2 we will determine the contribution of these Rac proteins to breast cancer metastasis in vivo. These approaches should allow us to validate Rac-controlled signaling proteins as novel therapeutic targets for metastatic breast cancer. The research performed in the first two years of funding has largely consisted of scaling technical obstacles. However we have now identified a CXCL12-responsive metastatic breast carcinoma cell line and have obtained results indicating that Rac1 and Rac1b play distinct roles in cell proliferation and cellular signaling events.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2007
- Accession Number
- ADA473355
Entities
People
- Marc Symons
Organizations
- North Shore University Hospital