title: IRF5 promotes the proliferation of human thyroid cancer cells.
abstract: BACKGROUND
  Interferon Regulatory Factor 5 is a transcription factor that regulates the expression of genes involved in the response to viral infection and in the stimulation of the immune system. Moreover, multiple studies have demonstrated that it negatively regulates cell growth and oncogenesis, favoring cell differentiation and apoptosis.Thyroid carcinoma represents 98% of all thyroid malignancies and has shown a steady increase in incidence in both the USA and western European countries.
  
  
  RESULTS
  We investigated the expression, localization and function of IRF5 in thyroid cancer cells and found that it is highly expressed in both primary and immortalized thyroid carcinomas but not in normal thyrocytes. IRF5 levels were variably modulated by Interferon alpha but IRF5 only localized in the cytoplasmic compartment, thus failing to induce p21 expression as previously reported in different cell models. Furthermore, ectopic IRF5 increased both the proliferation rate and the clonogenic potential of malignant thyroid cells, protecting them from the cytotoxic effects of DNA-damaging agents. These results were directly attributable to IRF5, as demonstrated by the reduction in colony-forming ability of thyroid cancer cells after IRF5 silencing. An IRF5-dependent induction of endogenous B-Raf observed in all thyroid cancer cells might contribute to these unexpected effects.
  
  
  CONCLUSIONS
  These findings suggest that, in thyroid malignancies, IRF5 displays tumor-promoting rather than tumor-suppressor activities.
authors.affiliation: Department of Clinical and Molecular Bio-Medicine, University of Catania, Via Androne, 83-95124 Catania, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Massimino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vigneri
authors.forename: Manuela
authors.initials: M
authors.lastname: Fallica
authors.forename: Annamaria
authors.initials: A
authors.lastname: Fidilio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Aloisi
authors.forename: Francesco
authors.initials: F
authors.lastname: Frasca
authors.forename: Livia
authors.initials: L
authors.lastname: Manzella
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D048493:Proto-Oncogene Proteins B-raf