The activation of the Sox2 RR2 pluripotency transcriptional reporter in human breast cancer cell lines is dynamic and labels cells with higher tumorigenic potential

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).-- et al.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 offin 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.This work is supported by grants from Obra Social Kutxa, Gobierno Vasco (Saiotek program and Consejería de Educación PI2010-25), and Instituto de Salud Carlos III Acción Estratégica en Salud (PI2010-01035). Work in Atanasio Pandiella lab is supported by the MINECO (BFU2012-39151).Peer Reviewe