GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes.
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.
Hoene
V
V
Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Fischer
M
M
Ivanova
A
A
Wallach
T
T
Berthold
F
F
Dame
C
C
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
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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