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.
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.
authors.affiliation: Regulation of Cell Growth Laboratory, Fundacion Inbiomed , San Sebastian , Spain ; Synpromics Ltd , Edinburgh , UK.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Iglesias
authors.affiliation: Regulation of Cell Growth Laboratory, Fundacion Inbiomed , San Sebastian , Spain ; StemTek Therapeutics , Bilbao , Spain.
authors.forename: Olatz
authors.initials: O
authors.lastname: Leis
authors.affiliation: Regulation of Cell Growth Laboratory, Fundacion Inbiomed , San Sebastian , Spain.
authors.forename: Estíbaliz
authors.initials: E
authors.lastname: Pérez Ruiz
authors.affiliation: Regulation of Cell Growth Laboratory, Fundacion Inbiomed , San Sebastian , Spain ; StemTek Therapeutics , Bilbao , Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gumuzio Barrie
authors.affiliation: Computational Genomics Institute, Centro de Investigación Principe Felipe (CIPF) , Valencia , Spain ; Functional Genomics Node, Centro de Investigación Principe Felipe (CIPF), Spanish National Institute of Bioinformatics (INB) , Valencia , Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-Garcia
authors.affiliation: Regulation of Cell Growth Laboratory, Fundacion Inbiomed , San Sebastian , Spain.
authors.forename: Ariane
authors.initials: A
authors.lastname: Aduriz
authors.affiliation: Regulation of Cell Growth Laboratory, Fundacion Inbiomed , San Sebastian , Spain.
authors.forename: Izaskun
authors.initials: I
authors.lastname: Beloqui
authors.affiliation: Instituto de Biología Molecular y Celular del Cancer , Salamanca , Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Hernandez-Garcia
authors.affiliation: Regulation of Cell Growth Laboratory, Fundacion Inbiomed , San Sebastian , Spain.
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Lopez-Mato
authors.affiliation: Computational Genomics Institute, Centro de Investigación Principe Felipe (CIPF) , Valencia , Spain ; Functional Genomics Node, Centro de Investigación Principe Felipe (CIPF), Spanish National Institute of Bioinformatics (INB) , Valencia , Spain ; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Valencia , Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Instituto de Biología Molecular y Celular del Cancer , Salamanca , Spain.
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology (ICO) , Girona , Spain ; Girona Biomedical Research Institute (IDIBGi) , Girona , Spain.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menendez
authors.affiliation: Regulation of Cell Growth Laboratory, Fundacion Inbiomed , San Sebastian , Spain ; StemTek Therapeutics , Bilbao , Spain.
authors.forename: Angel Garcia
authors.initials: AG
authors.lastname: Martin
keywords: EMT; Sox2; breast cancer stem cell; pluripotency; reporter