Inhibition of the translocated c-myc in Burkitt's lymphoma by a PNA complementary to the E mu enhancer.
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.
Cutrona
Giovanna
G
Division of Medical Oncology C, National Cancer Research Institute, Istituto Superiore di Sanità, Largo R. Benzi 10, 16132 Genoa, Italy. giovanna.cutrona@istge.it
Carpaneto
Elisabetta M
EM
Ponzanelli
Anna
A
Ulivi
Massimo
M
Millo
Enrico
E
Scarfì
Sonia
S
Roncella
Silvio
S
Benatti
Umberto
U
Boffa
Lidia C
LC
Ferrarini
Manlio
M
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005803:Genes, Immunoglobulin / Q000235:genetics*; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D020135:Peptide Nucleic Acids / Q000235:genetics / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D020135:Peptide Nucleic Acids; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors