Olf/EBF proteins are expressed in neuroblastoma cells: potential regulators of the Chromogranin A and SCG10 promoters
Autor: | Jens M. Nygren, Håkan Axelson, Christina Manetopoulos, Ramiro Gisler, Anna Lagergren, Mikael Sigvardsson, Paula Persson |
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Rok vydání: | 2004 |
Předmět: |
endocrine system
Cancer Research medicine.medical_specialty Neurite Cellular differentiation Neuroblastoma Internal medicine Gene expression medicine Chromogranins Neurites Humans Nerve Growth Factors Promoter Regions Genetic Transcription factor Neurons Binding Sites biology Stem Cells Chromogranin A Membrane Proteins Promoter DNA medicine.disease Molecular biology DNA-Binding Proteins Endocrinology Oncology Membrane protein biology.protein Trans-Activators Stathmin HeLa Cells |
Zdroj: | International journal of cancer. 110(1) |
ISSN: | 0020-7136 |
Popis: | The childhood malignancy neuroblastoma is derived from developmentally arrested sympathetic nervous system precursor cells. To obtain further insight into the molecular processes involved in the formation of these tumors, we decided to investigate the functional role of Olf/EBF (O/E) transcription factors in human neuroblastoma cells. We here report that O/E-1 and O/E-2 are expressed at variable levels in neuroblastoma cell lines and that O/E proteins could be identified by electrophoretic mobility shift assays. To identify potential neuronal target genes for O/E proteins in neuroblastoma cells we investigated the ability of a set of neuronal promoters to interact with O/E-1 in electrophoretic mobility shift assays. This analysis suggested that the Chromogranin A (CgA) and SCG10 promoters both contained binding sites for O/E-1. O/E-1 was able to activate the CgA promoter in vivo and mutation of the O/E-1 binding site in the CgA promoter reduced the functional activity of the element to about 60% of the wild-type in neuroblastoma cells, supporting the idea that O/E proteins may be involved in the control of the CgA promoter. Furthermore, overexpression of O/E-1 in hippocampal progenitor cells led to neurite outgrowth, indicative of a role for O/E proteins in neuronal differentiation. |
Databáze: | OpenAIRE |
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