title: Expression and prognostic significance of the autoimmune regulator gene in breast cancer cells.
abstract: The autoimmune regulator gene (AIRE) plays a fundamental role in tolerance by promoting the expression of tissue-specific antigens in medullary thymic epithelial cells (mTECs). Recently, AIRE expression was detected also in human keratinocytes and in tumors originating in stratified epithelia. Here, we tested whether AIRE is expressed in cancer cells. We analyzed AIRE expression in cancer cases from The Cancer Genome Atlas (TCGA) RNA-seq dataset and we found association with better outcome. AIRE protein expression was verified by immunohistochemistry in a cohort of 39 human breast cancer specimens and its prognostic relevance was confirmed in microarray-based gene expression data set NKI-295 and KM-Plotter. Both in the RNA-seq and gene expression datasets analyzed, AIRE expression was an independent strong prognostic factor for relapse-free survival (RFS), particularly in estrogen receptor-positive tumors. Enrichment of translation-related pathways was observed in AIRE-expressing tumors by Ingenuity Pathway Analysis and a significant increase of cells in G1 phase and activation of caspase cascades was induced by AIRE transfection in breast cancer luminal cell lines, suggesting that AIRE-induced over-translation of proteins lead to cycle arrest and apoptosis. These data are the first to identify AIRE expression in breast cancer and an association with prognosis.
authors.affiliation: a Dipartimento di Scienze Biomediche per la Salute , Università degli Studi di Milano , Milan , Italy.|b Molecular Targeting Unit , Department of Experimental Oncology and Molecular Medicine , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchi
authors.affiliation: a Dipartimento di Scienze Biomediche per la Salute , Università degli Studi di Milano , Milan , Italy.|b Molecular Targeting Unit , Department of Experimental Oncology and Molecular Medicine , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Sommariva
authors.affiliation: c Department of Experimental Oncology and Molecular Medicine , Functional Genomics Core Facility, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Loris
authors.initials: L
authors.lastname: De Cecco
authors.affiliation: b Molecular Targeting Unit , Department of Experimental Oncology and Molecular Medicine , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Triulzi
authors.affiliation: d Oncogenomics Laboratory, National Institute of Genomics Medicine , Mexico City , Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Cordoba
authors.affiliation: b Molecular Targeting Unit , Department of Experimental Oncology and Molecular Medicine , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Elda
authors.initials: E
authors.lastname: Tagliabue
authors.affiliation: a Dipartimento di Scienze Biomediche per la Salute , Università degli Studi di Milano , Milan , Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Sfondrini
authors.affiliation: a Dipartimento di Scienze Biomediche per la Salute , Università degli Studi di Milano , Milan , Italy.|b Molecular Targeting Unit , Department of Experimental Oncology and Molecular Medicine , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Balsari
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein
keywords: AIRE; Apoptosis; Breast Cancer; Cell-cycle arrest; TCGA; Transcription Factor