Gene expression profiles of human breast cancer cell lines

Numerous epithelial-to-mesenchymal transition (EMT)-promoting transcription factors have been implicated in tumorigenesis or metastasis, as well as chemoresistance of cancer. However, the underlying mechanism mediating these processes is unclear. Here we report that Foxq1, a forkhead box-containing transcription factor and EMT-inducing gene, promotes stemness traits and chemoresistance in mammary epithelial cells. We identify Twist1, Zeb2, and PDGFRα and β as Foxq1 downstream targets using an expression profiling assay. Further studies reveal that PDGFRα and β can be directly regulated by Foxq1, or indirectly through Twist1. Knockdown of both PDGFRα and β shows more significant effects on reversing Foxq1-promoted oncogenesis in vitro and in vivo than knockdown by either PDGFRα or β alone. PDGFRβ, but not PDGFRα, shows potent effects in reversing Foxq1-promoted stemness traits. Moreover, pharmacological inhibition or gene silencing of PDGFRs sensitize mammary epithelial cells to chemotherapeutic agents in vitro and in vivo. These findings collectively indicate PDGFRs as critical mediators underlying breast cancer tumorigenesis and chemoresistance driven by EMT promoting genes, which have potential clinical implications for cancer therapy. The purpose of these experiments is to investigate the downstream targets of several transcriptional factors including Foxq1 and IRX5. Another purpose is to compare the expression pattern between basal-like breast cancer cells including MDA-MB231, SUM159 and SUM1315.