Poster Sessions

CANCER-32

Hiroshi Yagi

H. Yagi, W. Tan, A. Molinolo, J.S. Gutkind

The GEP Oncogene, G alpha 12/13, Is Required for CXCR4-mediated Breast Cancer Metastasis

Recent studies suggest that chemokine SDF-1 and its seven transmembrane G protein coupled receptor, CXCR4, are involved in breast cancer metastasis. Of interest, recent gene expression analysis suggests that the expression of the GEP oncogene, encoding the alpha subunit of the heterotrimeric G proteins G alpha 12/13, correlates with the metastatic potential of many highly prevalent cancers including breast, prostate and oral cancer. In the current study, we took advantage of the abundant expression of CXCR4 in the breast cancer cell line MDA-MB231 to examine the contribution of G alpha 12/13 in metastasis mediated by the SDF-1/ CXCR4 signaling system. We observed that G alpha 12/13, not G alpha i, plays a pivotal role in the migration of MDA-MB231 cells in response to SDF-1 through CXCR4, likely due to the activation of Rho. Furthermore, orthotopical implantation of MDA-MB231 cells into mammary fat pad of SCID mice revealed that knock-down of the expression of G alpha 12/13 impairs the metastatic spread of these cells. Taken together, our findings provide evidence that the protein product of the GEP oncogene, G alpha 12/13, and its downstream targets are required for the breast cancer metastasis initiated by the activation of the chemokine receptor CXCR4.