c-myc Suppression in Burkitt's lymphoma cells.
The purpose of the study was to elucidate how DNA tetraplex (also referred to as G-quadruplex)-forming oligonucleotides mediate suppression of the human c-myc gene at the level of transcription initiation. A 22-base-long oligonucleotide, which is rich in guanines and folds into an intrastrand DNA tetraplex under physiological conditions, was administered to a Burkitt's lymphoma cell line overexpressing a (8:14) translocated c-myc allele. Administration of the oligonucleotide at nanomolar concentrations to the surrounding medium resulted in efficient cellular uptake, and was accompanied by a substantial concentration- and conformation-dependent decrease in growth rate. We discuss how c-myc transcription is initiated at the molecular level and speculate that the oligonucleotide exerts a dual effect on c-myc expression in vivo.
Simonsson
Tomas
T
Department of Molecular Biotechnology, Lunfberg Laboratory, Chalmers University of Technology, P.O. Box 462, SE 405 30 Göteborg, Sweden. tomas@mrc-lmb.cam.ac.uk
Henriksson
Marie
M
D000483:Alleles; D000970:Antineoplastic Agents / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D004247:DNA; D004305:Dose-Response Relationship, Drug; D054856:G-Quadruplexes; D016259:Genes, myc / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009841:Oligonucleotides / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002843:Chromatin; D009841:Oligonucleotides; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA