title: GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes.
abstract: BACKGROUND
  The aim of this study is to elucidate the expression patterns of GATA transcription factors in neuroblastoma and the developing sympathetic nervous system (SNS).
  
  
  METHODS
  GATA-2, -3 and -4 and their cofactor friend-of-GATA (FOG)-2 were investigated in primary neuroblastoma by immunohistochemistry, real-time RT-PCR (n=73) and microarray analysis (n=251). In addition, GATA-2, -3 and FOG-2 expression was determined by northern-blot hybridisation. In the developing murine SNS, Gata-4 and Fog-2 were examined by immunohistochemistry.
  
  
  RESULTS
  Although Gata-2, -3 and Fog-2 are expressed in the developing nervous system, Gata-4 was not detected. In contrast, protein expression of all factors was observed in human neuroblastoma. Northern-blot hybridisation and real-time RT-PCR suggested specific expression patterns of the four genes in primary neuroblastoma, but did not show unequivocal results. In the large cohort examined by microarrays, a significant association of GATA-2, -3 and FOG-2 expression with low-risk features was observed, whereas GATA-4 mRNA levels correlated with MYCN-amplification.
  
  
  CONCLUSIONS
  The transcription factors GATA-2 and -3, which are essential for normal SNS development, and their cofactor FOG-2 are downregulated in aggressive but not in favourable neuroblastoma. In contrast, upregulation of GATA-4 appears to be a common feature of this malignancy and might contribute to neuroblastoma pathogenesis.
authors.affiliation: Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Hoene
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Ivanova
authors.forename: T
authors.initials: T
authors.lastname: Wallach
authors.forename: F
authors.initials: F
authors.lastname: Berthold
authors.forename: C
authors.initials: C
authors.lastname: Dame
mesh_terms: D001923:Brain Chemistry; D004268:DNA-Binding Proteins / Q000032:analysis; D050980:GATA Transcription Factors / Q000032:analysis* / Q000235:genetics; D050989:GATA2 Transcription Factor / Q000032:analysis; D050990:GATA3 Transcription Factor / Q000032:analysis; D050991:GATA4 Transcription Factor / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D000071447:N-Myc Proto-Oncogene Protein; D009432:Neural Crest / Q000737:chemistry / Q000166:cytology; D009447:Neuroblastoma / Q000737:chemistry*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D013564:Sympathetic Nervous System / Q000737:chemistry; D014157:Transcription Factors / Q000032:analysis
chemical_list: D004268:DNA-Binding Proteins; D050980:GATA Transcription Factors; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C117427:ZFPM2 protein, human
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