PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma. (Articolo in rivista) (literal)

Anno

• 2010-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1371/journal.pone.0013108 (literal)

Alternative label

• Tiziana Bachetti; Daniela Di Paolo; Simona Di Lascio; Valentina Mirisola; Chiara Brignole; Marta Bellotti; Irene Caffa; Chiara Ferraris; Michele Fiore; Diego Fornasari; Roberto Chiarle; Silvia Borghini; Ulrich Pfeffer; Mirco Ponzoni; Isabella Ceccherini; Patrizia Perri (2010)
  PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma.
  in PloS one
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Tiziana Bachetti; Daniela Di Paolo; Simona Di Lascio; Valentina Mirisola; Chiara Brignole; Marta Bellotti; Irene Caffa; Chiara Ferraris; Michele Fiore; Diego Fornasari; Roberto Chiarle; Silvia Borghini; Ulrich Pfeffer; Mirco Ponzoni; Isabella Ceccherini; Patrizia Perri (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 5 (literal)

Rivista

• PloS one (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 10 (literal)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Laboratory of Molecular Genetics, G. Gaslini Children's Hospital, Genoa, Italy Experimental Therapy Unit, Laboratoty of Oncology, G. Gaslini Children's Hopsital, Genoa, Italy Dept. of Pharmacology, School of Medicine, Università degli Studi di Milano, Milan, Italy Advanced Molecular Diagnostics, National Cancer Research Institute, Genoa, Italy Experimental Therapy Unit, Laboratoty of Oncology, G. Gaslini Children's Hopsital, Genoa, Italy Advanced Molecular Diagnostics, National Cancer Research Institute, Genoa, Italy Experimental Therapy Unit, Laboratoty of Oncology, G. Gaslini Children's Hospital, Genoa, Italy Laboratory of Molecular Genetics, G. Gaslini Children's Hospital, Genoa, Italy Laboratory of Molecular Genetics, G. Gaslini Children's Hospital, Genoa, Italy Dept. of Pharmacology, School of Medicine, Università degli Studi di Milano, Milan, Italy - CNR, Institute of Neuroscience, Milan, Italy Dept. Biochemical Sciences and Human Oncology, University of Turin, Turin, Italy Laboratory of Molecular Genetics, G. Gaslini Children's Hospital, Genoa, Italy Advanced Molecular Diagnostics, National Cancer Research Institute, Genoa, Italy Experimental Therapy Unit, Laboratoty of Oncology, G. Gaslini Children's Hospital, Genoa, Italy Laboratory of Molecular Genetics, G. Gaslini Children's Hospital, Genoa, Italy Experimental Therapy Unit, Laboratoty of Oncology, G. Gaslini Children's Hospital, Genoa, Italy (literal)

Titolo

• PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma. (literal)

Abstract

• Background: Neuroblastoma (NB) is a severe pediatric tumor originating from neural crest derivatives and accounting for 15% of childhood cancer mortality. The heterogeneous and complex genetic etiology has been confirmed with the identification of mutations in two genes, encoding for the receptor tyrosine kinase Anaplastic Lymphoma Kinase (ALK) and the transcription factor Paired-like Homeobox 2B (PHOX2B), in a limited proportion of NB patients. Interestingly, these two genes are overexpressed in the great majority of primary NB samples and cell lines. These observations led us to test the hypothesis of a regulatory or functional relationship between ALK and PHOX2B underlying NB pathogenesis. Methodology/Principal Findings: Following this possibility, we first confirmed a striking correlation between the transcription levels of ALK, PHOX2B and its direct target PHOX2A in a panel of NB cell lines. Then, we manipulated their expression in NB cell lines by siRNA-mediated knock-down and forced over-expression of each gene under analysis. Surprisingly, PHOX2B- and PHOX2A-directed siRNAs efficiently downregulated each other as well as ALK gene and, consistently, the enhanced expression of PHOX2B in NB cells yielded an increment of ALK protein. We finally demonstrated that PHOX2B drives ALK gene transcription by directly binding its promoter, which therefore represents a novel PHOX2B target. Conclusions/Significance: These findings provide a compelling explanation of the concurrent involvement of these two genes in NB pathogenesis and are going to foster a better understanding of molecular interactions at the base of the disease. Moreover, this work opens new perspectives for NBs refractory to conventional therapies that may benefit from the design of novel therapeutic RNAi-based approaches for multiple gene targets. (literal)

Prodotto di

• Modulazione recettoriale del differenziamento cellulare (ME.P03.004.001) (Modulo)
• Istituto di neuroscienze (IN) (Istituto)

Autore CNR

• DIEGO MARIA MICHELE FORNASARI (Persona)

Insieme di parole chiave

• Parole chiave di "PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma." (Insieme di parole chiave)

Incoming links:

Prodotto

• Istituto di neuroscienze (IN) (Istituto)
• Modulazione recettoriale del differenziamento cellulare (ME.P03.004.001) (Modulo)

Autore CNR di

• DIEGO MARIA MICHELE FORNASARI (Persona)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• PloS one (Rivista)

Insieme di parole chiave di

• Parole chiave di "PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma." (Insieme di parole chiave)