Olf/EBF proteins are expressed in neuroblastoma cells: potential regulators of the Chromogranin A and SCG10 promoters.
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.
Persson
Paula
P
Department of Laboratory Medicine, Division of Molecular Medicine, Lund University, University Hospital MAS, Malmö, Sweden.
Manetopoulos
Christina
C
Lagergren
Anna
A
Nygren
Jens
J
Gisler
Ramiro
R
Axelson
Håkan
H
Sigvardsson
Mikael
M
D001665:Binding Sites; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D009414:Nerve Growth Factors / Q000235:genetics*; D016501:Neurites / Q000502:physiology; D009447:Neuroblastoma / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D011401:Promoter Regions, Genetic; D050777:Stathmin; D013234:Stem Cells / Q000502:physiology; D015534:Trans-Activators / Q000032:analysis / Q000502:physiology*
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D004268:DNA-Binding Proteins; C081976:EBF1 protein, human; D008565:Membrane Proteins; D009414:Nerve Growth Factors; C063314:STMN2 protein, human; D050777:Stathmin; D015534:Trans-Activators; D004247:DNA