Cell Growth Arrest Mediated by STAT Proteins in Breast Cancer Cells

摘要

STAT3 has been demonstrated to be an oncogene. To address the STAT3 function in cell growth and cell survival, we have disrupted the STAT3 gene in mice specifically in hepatocytes, endothelial cells or dendritic cells using a bacteriophage Cre/loxP system. We have induced STAT3-deletion exclusively in these cells by crossing a STAT3-floxed mouse with a transgenic mouse expressing Cre under the control of transthyretin, Tie-2 and CDllb promoters, respectively. No specific phenotypes have been identified in STAT3 null cells yet. In addition, to analyze the downstream gene regulation by STAT, we have established representational difference analysis (RDA). We have analyzed the gene regulation in B lymphocytes upon B-cell receptor cross-linking. Furthermore, we have started DNA microarray analysis. Moreover, to address the Task3 (Month 25 - 36), we examined STAT activation in response to neuregulin and platelet-derived growth factor (PDGF) in NIH 3T3 cells. However, we did not find clear correlations between STAT activation and cell growth. Based on these findings, we are planning to further investigate the STAT function in cell growth regulation focusing on analysis of the downstream gene regulation.