Isolation and characterization of human breast cancer cells with SOX2 promoter activity

Sex determining region Y-box 2 (SOX2) is well known as one of the "sternness" factors and is often expressed in cancers including breast cancer. In this study, we developed a reporter system using fluorescent protein driven by the promoter for SOX2 gene to detect and isolate living SOX2-positive cells. Using this system, we determined that SOX2 promoter activities were well correlated with SOX2 mRNA expression levels in 5 breast cancer cell lines, and that the cell population with positive SOX2 promoter activity (pSp-T+) isolated from one of the 5 cell lines, MCF-7 cells, showed a high SOX2 protein expression and high sphere-forming activity compared with very low promoter activity (pSp-Tlow/-). The pSp-T(+)pbpulation expressed higher mRNA levels of several stemness-related genes such as CD44, ABCB1, NANOG and TWIST] than the pSp-Tlow/- population whereas the two populations expressed CD24 at similar levels. These results suggest that the cell population with SOX2 promoter activity contains cancer stem cell (CSC)-like cells which show different expression profiles from those of CSC-marker genes previously recognized in human breast cancers. (C) 2013 Elsevier Inc. All rights reserved

Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1 alpha-MUC1 pathway

In this study, we examined the effects of hypoxia on the malignancy of human malignant pleural mesothelioma (MPM) cell lines, and found (I) hypoxia enhanced motility and invasiveness of human malignant pleural mesothelioma (MPM) cells; (2) this phenomenon resulted from increased expression of sialylated MUC1 through the activation of HIF-1 pathway; (3) two HIF-binding sites located in the promoter region of MUC1 were important for MUC1 transactivation under hypoxia. These findings are useful for better understanding molecular mechanisms of aggressive behavior of MPM cells and for targeting them in the clinical therapies for MPM patients