Inhibition of the translocated c-myc in Burkitt's lymphoma by a PNA complementary to the E mu enhancer

Cancer Res. 2003 Oct 1;63(19):6144-8.

Abstract

In Burkitt's Lymphoma there is an up-regulation of the c-myc oncogene caused by its translocation from chromosome 8 to chromosome 14, often close to the E mu enhancer of the immunoglobulin heavy chain locus (IgH). In Burkitt's Lymphoma cells, a peptide nucleic acid complementary for a specific unique E mu intronic sequence selectively blocked the expression of the c-myc oncogene under E mu control but not of other c-myc alleles. This Peptide Nucleic Acid also inhibited IgM expression in B cells. The finding that PNAs specific for a regulatory noncoding sequence can block gene expression has important conceptual and practical implications.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Burkitt Lymphoma / drug therapy
  • Burkitt Lymphoma / genetics*
  • Burkitt Lymphoma / metabolism
  • Cell Division / drug effects
  • Cell Division / genetics
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Immunoglobulin / genetics*
  • Genes, myc / drug effects
  • Genes, myc / genetics*
  • Humans
  • Peptide Nucleic Acids / genetics
  • Peptide Nucleic Acids / pharmacology*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics
  • Translocation, Genetic

Substances

  • Core Binding Factor Alpha 2 Subunit
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Peptide Nucleic Acids
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors