Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression.
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.


CONCLUSIONS
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.
Lagergren
Anna
A
Stem Cell Center, Lund University, S-221 85 Lund, Sweden. Anna.Lagergren@stemcell.lu.se <Anna.Lagergren@stemcell.lu.se>
Manetopoulos
Christina
C
Axelson
Håkan
H
Sigvardsson
Mikael
M
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D051925:CD79 Antigens; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024002:HMGB Proteins / Q000378:metabolism; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051757:PAX5 Transcription Factor; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D018941:Antigens, CD19; D051925:CD79 Antigens; C497881:CD79A protein, human; D004268:DNA-Binding Proteins; C081976:EBF1 protein, human; D024002:HMGB Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D011947:Receptors, Antigen, B-Cell; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors