AUTHOR=Iglesias Juan Manuel , Leis Olatz , Pérez Ruiz Estíbaliz , Gumuzio Barrie Juan , Garcia-Garcia Francisco , Aduriz Ariane , Beloqui Izaskun , Hernandez-Garcia Susana , Lopez-Mato Maria Paz , Dopazo Joaquin , Pandiella Atanasio , Menendez Javier A. , Martin Angel Garcia TITLE=The Activation of the Sox2 RR2 Pluripotency Transcriptional Reporter in Human Breast Cancer Cell Lines is Dynamic and Labels Cells with Higher Tumorigenic Potential JOURNAL=Frontiers in Oncology VOLUME=4 YEAR=2014 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2014.00308 DOI=10.3389/fonc.2014.00308 ISSN=2234-943X ABSTRACT=

The striking similarity displayed at the mechanistic level between tumorigenesis and the generation of induced pluripotent stem cells and the fact that genes and pathways relevant for embryonic development are reactivated during tumor progression highlights the link between pluripotency and cancer. Based on these observations, we tested whether it is possible to use a pluripotency-associated transcriptional reporter, whose activation is driven by the SRR2 enhancer from the Sox2 gene promoter (named S4+ reporter), to isolate cancer stem cells (CSCs) from breast cancer cell lines. The S4+ pluripotency transcriptional reporter allows the isolation of cells with enhanced tumorigenic potential and its activation was switched on and off in the cell lines studied, reflecting a plastic cellular process. Microarray analysis comparing the populations in which the reporter construct is active versus inactive showed that positive cells expressed higher mRNA levels of cytokines (IL-8, IL-6, TNF) and genes (such as ATF3, SNAI2, and KLF6) previously related with the CSC phenotype in breast cancer.