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

BMC Cancer. 2004 Nov 15:4:80. doi: 10.1186/1471-2407-4-80.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, CD19 / genetics
  • Antigens, CD19 / metabolism*
  • B-Lymphocytes / metabolism
  • CD79 Antigens
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HMGB Proteins / metabolism
  • Humans
  • Lymphoma, B-Cell / metabolism*
  • Neuroblastoma / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • PAX5 Transcription Factor
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • TCF Transcription Factors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Antigens, CD
  • Antigens, CD19
  • CD79 Antigens
  • CD79A protein, human
  • DNA-Binding Proteins
  • EBF1 protein, human
  • HMGB Proteins
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • Receptors, Antigen, B-Cell
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors