title: Role of JMJD6 in Breast Tumourigenesis.
abstract: BACKGROUND
  Protein arginine methylation is a common post translational modification that regulates protein properties. This modification is carried out by a family of nine arginine methyltransferases (PRMTs). Arginine methylation has already been linked to tumourigenesis as overexpression of these enzymes was associated with various cancers, notably in breast cancers. Since the Jumonji Domain Containing 6 protein (JMJD6) possesses an arginine demethylase activity able to remove the methyl mark, we wanted to assess its potential role in breast tumourigenesis.
  
  
  METHODS
  The expression of the protein by tissue microarray immunohistochemical staining was performed on a cohort of 133 breast tumours. Using cell lines stably overexpressing or knocked down for JMJD6, we evaluated its role on cell proliferation, cell migration, colony formation and mice tumour xenografts.
  
  
  RESULTS
  The analysis of JMJD6 expression in a cohort of breast tumour samples indicates that JMJD6 was highly expressed in aggressive breast tumours. Moreover, high expression of JMJD6 was associated with poor disease-free survival of patients in this cohort. JMJD6 silencing in breast tumoural cells promotes certain characteristics of tumourigenesis including proliferation, migration in vitro, and tumour growth in vivo. These effects are dependent on its demethylase activity as an enzymatic dead mutant lost these properties.
  
  
  CONCLUSIONS
  Although JMJD6 displays anti-tumoral properties in cell lines, its expression in breast tumours may be a marker of poor prognosis, suggesting that its function could be altered in breast cancer.
authors.affiliation: Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69000 Lyon, France; Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; Equipe Labellisée "La Ligue.
authors.forename: Coralie
authors.initials: C
authors.lastname: Poulard
authors.affiliation: Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69000 Lyon, France; Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; Equipe Labellisée "La Ligue.
authors.forename: Juliette
authors.initials: J
authors.lastname: Rambaud
authors.affiliation: Centre Léon Bérard, Biostatistics Unit, F-69000 Lyon, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lavergne
authors.affiliation: Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69000 Lyon, France; Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; Equipe Labellisée "La Ligue.
authors.forename: Julien
authors.initials: J
authors.lastname: Jacquemetton
authors.affiliation: UMR CNRS 8203 Vectorology and anti-cancer therapeutics, Institut Gustave Roussy, 114, Rue E. Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
authors.affiliation: Centre Léon Bérard, Department of Medical Oncology, F-69000 Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Trédan
authors.affiliation: Centre Léon Bérard, Biostatistics Unit, F-69000 Lyon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chabaud
authors.affiliation: Centre Léon Bérard, Pathology Department, F-69000 Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.affiliation: Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69000 Lyon, France; Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; Equipe Labellisée "La Ligue.
authors.forename: Laura
authors.initials: L
authors.lastname: Corbo
authors.affiliation: Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69000 Lyon, France; Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; Equipe Labellisée "La Ligue.
authors.forename: Muriel
authors.initials: M
authors.lastname: Le Romancer
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis
chemical_list: C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases