Abstract
GATA transcription factors, important for cell differentiation and proliferation, have been detected in various normal tissues, but also in neoplasia. Deregulation or mutation of transcription factors might be crucial for the formation of neuroblastoma, a tumor deriving from the developing sympathetic nervous system. While GATA-2, -3, -6 and FOG-2 have been described in the central and peripheral nervous system with GATA-2 and -3 being essential for the development of sympathetic neurons, GATA-4 is not expressed in the normal developing or adult brain nor in the sympathetic nervous system. Microarray analyses of a large cohort of primary neuroblastoma specimens (n = 251) confirmed GATA-4 expression in this malignancy with higher mRNA levels in MYCN-amplified (n = 32) vs. MYCN-nonamplified (n = 218) tumors. In contrast, GATA-2, -3, -6 and FOG-2 were highly expressed in tumors with low-risk features, as in MYCN-nonamplified tumors, tumors of localized stages and of stage 4S, tumors of younger patients and those with a lower risk according to a highly accurate gene-expression based classifier (PAM algorithm). Together, the data provide further evidence that proteins which are essential for the development of the sympathetic nervous system are downregulated in aggressive but not in favorable neuroblastoma. First functional data recently indicated that GATA-3 regulates cellular proliferation of neuroblastoma cells by activating Cyclin D1. In contrast, GATA-4 appears to be induced during tumorigenesis and might contribute to neuroblastoma pathogenesis. Thus, future studies will elucidate the implication of GATA factors and FOG-2 in neuroblastoma biology.
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Acknowledgment
We thank PD Dr. Matthias Fischer (Department of Pediatric Oncology and Hematology and Center for Molecular Medicine Cologne (CMMC), University of Cologne) for the discussion on the biology of GATA transcription factors in neuroblastoma. Our experimental work on GATA transcription factors in neuroblastoma has been supported by grants from the Fritz-Thyssen-Stiftung, the Berliner Krebsgesellschaft e.V. and the Verein für Frühgeborene Kinder an der Charité e.V.
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Hoene, V., Dame, C. (2012). Neuroblastoma: Role of GATA Transcription Factors. In: Hayat, M. (eds) Neuroblastoma. Pediatric Cancer, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2418-1_14
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DOI: https://doi.org/10.1007/978-94-007-2418-1_14
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