Role of Rac GTPases in Chemokine-Stimulated Breast Carcinoma Metastasis
Annual rept. 1 Jul 2007-30 Jun 2008
NORTH SHORE-LIJ RESEARCH INST MANHASSET NY
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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 aimed to test the hypothesis that Rac proteins are essential for CXCR4-mediated breast carcinoma cell proliferation and survival, thereby contributing to breast cancer metastasis. In Task 1, we have investigated the role of Rac proteins in CXCL12- regulated breast carcinoma cell proliferation and survival in vitro. We have focused our analysis on a novel splice form of Rac1 that is induced during breast cancer progression. Our findings indicate that Rac1 and Rac1b play distinct roles in cell proliferation and cellular signaling events. In Task 2, we planned to determine the contribution of Rac proteins to breast cancer metastasis in vivo, but we had to terminate this line of research due to technical difficulties.
- Medicine and Medical Research