Role of Rac GTPases in Chemokine-Stimulated Breast Carcinoma
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 1, 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 this first year of funding largely pertains to Task 1. We showed that CXCL12 stimulates Rac1 activity in breast carcinoma cells, suggesting that Rac1 is likely to play a role in CXCL12- mediated functions in these cells. We also discuss efforts to specifically downregulate the Rac1b splice form.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2006
- Accession Number
- ADA457469
Entities
People
- Marc H. Symons
Organizations
- North Shore University Hospital