Study of the role of the SOX2 transcription factor in neural and mammary cancer stem cells using SOX2 conditional knock-out in mouse

The stem cell-determining transcription factor Sox2 is required for the maintenance of normal stem cells. In this study, we investigated the requirement for Sox2 in neural and breast cancer stem-like cells. In the first case, using a conditional genetic deletion mutant in a mouse model of platelet-derived growth factor-induced malignant oligodendroglioma. Taken together, our results showed that Sox2 is essential for tumor initiation by mouse pHGG cells, and we illustrated a Sox2-directed strategy of immunotherapy to eradicate tumor-initiating cells. In the second case, we used a Sox2 conditional deletion by an MMTV-Cre transgene (active in mammary tissue) to address Sox2 requirement within a widely studied mouse model of mammary tumor, produced by expression of a transgene encoding a mutated ErbB2/Neu oncogene, driven to mammary tissue by the MMTV promoter. Our results point to a heterogeneity within mammary tumors regarding Sox2 expression and function, in particular within ErbB2/Neu-positive tumors, that it will be important to consider when hypothesizing therapy approaches.