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Updated: Aug 7, 2026

Zebrafish Model of Neuroblastoma Metastasis
Published on: March 14, 2021
Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted
Anna Lagergren1, Christina Manetopoulos, Håkan Axelson
1Stem Cell Center, Lund University, S-221 85 Lund, Sweden. Anna.Lagergren@stemcell.lu.se <Anna.Lagergren@stemcell.lu.se>
Background:
Transcription factors are frequently involved in the process of cellular transformation, and many malignancies are characterized by a distinct genetic event affecting a specific transcription factor. This probably reflects a tissue specific ability of transcription factors to contribute to the generation of cancer but very little is known about the precise mechanisms that governs these restricted effects.
Methods:
To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR. The presence of transcription factors in the different model cell lines was further investigated by EMSA analysis.
Results:
In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins. We here show that neuroblastoma cells express these three, for B cell development crucial transcription factors, but nevertheless fail to express detectable levels of their known target genes. Expression of mb-1 could, however, be induced in neuroblastoma cells after disruption of the chromatin structure by treatment with 5-azacytidine and Trichostatin A.
Conclusion:
These data suggest that transcription factors are able to selectively activate target genes in different tissues and that chromatin structure plays a key role in the regulation of this activity.
Insights
Transcription factors like EBF regulate genes selectively. In neuroblastoma cells, chromatin structure, not transcription factor presence, prevents target gene activation, but can be overcome with specific treatments.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Transcription factors are crucial in cellular transformation and cancer development.
- Tissue-specific effects of transcription factors in cancer are not well understood.
- Mechanisms governing restricted transcription factor activity remain largely unknown.
Purpose of the Study:
- To investigate the selectivity of transcription factor target gene activation.
- To compare gene expression patterns for the transcription factor EBF in lymphoma and neuroblastoma.
- To elucidate the role of chromatin structure in regulating transcription factor activity.
Main Methods:
- Micro-array analysis for overall gene expression patterns.
- RT-PCR to assess target gene expression for EBF.
- Electrophoretic Mobility Shift Assay (EMSA) to detect transcription factor presence.
Main Results:
- EBF-1, Pax-5, and E-proteins regulate mb-1 and CD19 in pre-B cells.
- Neuroblastoma cells express these key transcription factors but lack target gene expression.
- Chromatin disruption via 5-azacytidine and Trichostatin A induced mb-1 expression in neuroblastoma.
Conclusions:
- Transcription factors exhibit selective target gene activation across different tissues.
- Chromatin structure is a critical regulator of transcription factor activity.
- Epigenetic modifications can restore transcription factor function in cancer cells.
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