Figure 7

STAT5 expression in human breast cancer is generally associated with increased differentiation. In human breast cancer tissue, STAT5 expression has been reproducibly associated with increased differentiation and a better prognosis and response to endocrine therapy. Experiments that alter STAT5 expression levels in breast cancer cell lines revealed a link between the presence of STAT5 and increased differentiation in BT-20, T47D, and MDA-MB-468 breast cancer cell lines. Increased cell motility, invasiveness, and migration are behaviors that can be found in association with decreased differentiation. In MCF-7 andT47D cells lines, STAT5 inhibits motility, and in the T47D cell line loss of STAT5 increases invasiveness and this is consistent with the correlation between STAT5 and increased differentiation. However, in MDA-MB-231 and BT-549, loss of STAT5 actually inhibits migration. Increased sensitivity to therapy is considered a good prognostic sign, and in the MDA-MB-468 cell line, STAT5 is correlated with increased sensitivity to paclitaxel and vinorelbine. However, in SKBR3, MCF-7, and T47D cell lines, experiments have correlated the presence of STAT5 with increased cell survival and, in T47D cells, resistance to tamoxifen and, in SKBR3 cells, a decreased response to trastuzumab. In SKBR3 and MD-MBA-231 cells, loss of STAT5 is actually correlated with growth inhibition. These sometimes consistent and sometimes conflicting results in different breast cancer cell lines indicate that the relative impact of STAT5 on cell differentiation, survival, and proliferation can be cell line-specific. BCL6 gene expression and activating protein-1 (AP-1) signaling are reduced by increased STAT5 signaling and increased by reduced STAT5 signaling. Identified downstream STAT5 genes in breast cancer cells include heat shock protein 90-A (HSP90A), insulin growth factor (IGF), and cyclin D1. BCL6, proto-oncogene B-cell chronic lymphocytic leukemia/lymphoma 6; STAT5, signal transducer and activator of transcription 5.