Abstract 4224: Sox2 control breast cancer stem-like cells in a breast carcinoma cell line

Abstract

Abstract Many solid tumors, including breast cancer, exhibit a functional hierarchy of cells of which only a small subpopulation of stem-like cells can give rise to the differentiated cells that make the bulk of the tumor. Recently, a method for the culture of undifferentiated human mammary epithelial cells in non-adherent “mammospheres” has been described. Mammospheres are enriched in stem/progenitor cells giving rise to all three mammary cell types. Although gene profiling was used to compare sphere cells to differentiated cells, no specific markers were described. Three main transcription factors: Oct4, Sox2 and Nanog, have probed responsible for maintaining the undifferentiated state of stem cells, particularly embryonic stem cells. Ectopic introduction of these factors into differentiated cells is capable of reprogramming these cells into embryonic stem-like cells (called iPS, induced pluripotent stem cells). It has been shown recently that one of the main regulators of oncogenic transformation, the p53 tumor supressor, controls the induction of pluripotency, thus linking the process of reprogramming with the process of tumorigenesis. By characterizing factors that control mammosphere formation in the breast carcinoma cell line MCF7 we have identified Sox2 as a gene that is up-regulated upon sphere formation. Besides, ectopic expression of Sox2 is capable of inducing augmented sphere formation, suggesting that expression of Sox2 is a key regulator of breast cancer stem cell phenotype. Up-regulation of Sox2 expression is transcriptionally controlled at the level of the RR1 Sox2 promoter enhancer which is also involved in regulation of Sox2 expression in pluripotent stem cell lines. The recent observation that the tumor suppressor p53 pathway acts as a barrier for induced pluripotency reprogramming has lead to the speculation that cancer stem cells may arise through an altered reprogramming-like mechanism. Our data suggests that Sox2 expression may be such an event. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4224.