title: RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes.
abstract: Runx1 participation in epithelial mammary cells is still under review. Emerging data indicates that Runx1 could be relevant for breast tumor promotion. However, to date no studies have specifically evaluated the functional contribution of Runx1 to control gene expression in mammary epithelial tumor cells. It has been described that Runx1 activity is defined by protein context interaction. Interestingly, Foxp3 is a breast tumor suppressor gene. Here we show that endogenous Runx1 and Foxp3 physically interact in normal mammary cells and this interaction blocks Runx1 transcriptional activity. Furthermore we demonstrate that Runx1 is able to bind to R-spondin 3 (RSPO3) and Gap Junction protein Alpha 1 (GJA1) promoters. This binding upregulates Rspo3 oncogene expression and downregulates GJA1 tumor suppressor gene expression in a Foxp3-dependent manner. Moreover, reduced Runx1 transcriptional activity decreases tumor cell migration properties. Collectively, these data provide evidence of a new mechanism for breast tumor gene expression regulation, in which Runx1 and Foxp3 physically interact to control mammary epithelial cell gene expression fate. Our work suggests for the first time that Runx1 could be involved in breast tumor progression depending on Foxp3 availability.
authors.affiliation: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina.|Present Address: Oncology Institute "Angel H Roffo", Buenos Aires, Argentina.
authors.forename: María Sol
authors.initials: MS
authors.lastname: Recouvreux
authors.affiliation: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina.|Present Address: Immunopharmacology Laboratory, IQUIBICEN-CONICET, FCEN-UBA, Buenos Aires, Argentina.
authors.forename: Esteban Nicolás
authors.initials: EN
authors.lastname: Grasso
authors.affiliation: Department of Biologie Cellulaire, Universite de Geneve Sciences III, Geneve, Switzerland.
authors.forename: Pablo Christian
authors.initials: PC
authors.lastname: Echeverria
authors.affiliation: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina.|Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Rocha-Viegas
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Lucio Hernán
authors.initials: LH
authors.lastname: Castilla
authors.affiliation: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Schere-Levy
authors.affiliation: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina.
authors.forename: Johanna Melisa
authors.initials: JM
authors.lastname: Tocci
authors.affiliation: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina.|Departamento de Química Biológica, UBA, Buenos Aires, Argentina.
authors.forename: Edith Claudia
authors.initials: EC
authors.lastname: Kordon
authors.affiliation: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina.|Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rubinstein
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D018031:Connexin 43 / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011401:Promoter Regions, Genetic / Q000235:genetics; D019699:Thrombospondins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays; D000098907:R-Spondins
chemical_list: D018031:Connexin 43; D050676:Core Binding Factor Alpha 2 Subunit; D051858:Forkhead Transcription Factors; D019699:Thrombospondins; C418974:FOXP3 protein, human; C500216:GJA1 protein, human; C475438:RSPO3 protein, human; D000098907:R-Spondins; C493728:RUNX1 protein, human
keywords: Foxp3; GJA1; Rspo3; Runx1; gene expression regulation