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