期刊
BRITISH JOURNAL OF CANCER
卷 101, 期 8, 页码 1481-1489出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6605276
关键词
GATA; neuroblastoma; oncogene; sympathetic nervous system; transcription factor
类别
资金
- Sonnenfeld Stiftung (Berlin, Germany)
- Sanitatsrat Dr. Emil Alexander Hubner und Gemahlin-Stiftung (Stifterverband fur die Deutsche Wissenschaft e. V., Essen)
- Verein fur Fruhgeborene Kinder am Virchow-Klinikum e. V. (Berlin, Germany)
- Fritz - Thyssen - Stiftung [AZ. 10.05.2.162]
- Berliner Krebsgesellschaft [DAFF200829]
- Bundesministerium fur Bildung und Forschung [01GS0456]
- Jurgen - Manchot - Stiftung
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. CONCLUSION: 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. British Journal of Cancer (2009) 101, 1481-1489. doi: 10.1038/sj.bjc.6605276 www.bjcancer.com Published online 25 August 2009 (C) 2009 Cancer Research UK
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