Suppression of c-myc is a critical step in glucocorticoid-induced human leukemic cell lysis.
Glucocorticoids evoke cytolysis in clonal human leukemic CEM-C7 cells. Suppression of c-myc mRNA by dexamethasone closely correlates with cell lysis only in CEM clones with both glucocorticoid receptor and intact lysis functions. We tested the theory that c-myc repression is essential for glucocorticoid-induced lymphocytolysis by preventing down-regulation of c-myc gene in the presence of dexamethasone and by reducing c-myc mRNA levels with antisense oligonucleotides. We find that sustained expression of c-myc provides resistance to dexamethasone-induced lysis, and antisense c-myc oligomers induce cell lysis. The lethal effects of dexamethasone in these leukemic cells appear to involve reduction of c-myc below the levels required to maintain cellular growth and integrity.
Thulasi
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Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-0645.
Harbour
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DV
Thompson
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EB
D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc; D005822:Genetic Vectors; D006801:Humans; D007700:Kinetics; D007938:Leukemia; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology
D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003907:Dexamethasone; D015032:Zinc