title: TWIST1 is a direct transcriptional target of MYCN and MYC in neuroblastoma.
abstract: In neuroblastoma, MYCN amplification is associated with a worse prognosis and is a criterion used in the clinic to provide intensive treatments to children even with localized disease. In correlation with MYCN amplification, upregulation of TWIST1, a transcription factor playing a crucial role in inhibition of apoptosis and differentiation, was previously reported. Clinical data set analysis of MYCN, MYC and TWIST1 expression permits us to confirm that TWIST1 expression is upregulated in MYCN amplified neuroblastoma but also in a subset of neuroblastoma harboring high expression of MYCN or MYC without gene amplification. In silico analyses reveal the presence of several MYC regulatory motifs (E-Boxes and INR) within the TWIST1 promoter. Using gel shift assay and reporter activity assays, we demonstrate that both N-Myc and c-Myc proteins can bind and activate the TWIST1 promoter. Therefore, we propose TWIST1 as a direct MYC transcriptional target.
authors.affiliation: Université Lyon 1, F-69000 Lyon, France; INSERM UMR-S1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69008 Lyon, France.
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Selmi
authors.affiliation: Université Lyon 1, F-69000 Lyon, France; INSERM UMR-S1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69008 Lyon, France.
authors.forename: Maud
authors.initials: M
authors.lastname: de Saint-Jean
authors.affiliation: Centre Léon Bérard, F-69008 Lyon, France; Pôle des Sciences Cliniques, Lyon, F-69008, France.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Jallas
authors.affiliation: Centre Léon Bérard, F-69008 Lyon, France; Pôle des Sciences Cliniques, Lyon, F-69008, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Garin
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hogarty
authors.affiliation: CNRS UMR8126 Institut Gustave Roussy, Université Paris XI, Villejuif F-94805, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Bénard
authors.affiliation: Université Lyon 1, F-69000 Lyon, France; INSERM UMR-S1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69008 Lyon, France; Centre Léon Bérard, F-69008 Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
authors.affiliation: Université Lyon 1, F-69000 Lyon, France; INSERM UMR-S1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69008 Lyon, France; Centre Léon Bérard, F-69008 Lyon, France; Pôle des Sciences Cliniques, Lyon, F-69008, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: Université Lyon 1, F-69000 Lyon, France; Centre Léon Bérard, F-69008 Lyon, France; Pôle des Sciences Cliniques, Lyon, F-69008, France. Electronic address: sandrine.wittmann@lyon.unicancer.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Valsesia-Wittmann
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C489427:MYC protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1
keywords: MYC; MYCN; TWIST1; Transcriptional regulation neuroblastoma