Apoptosis induced by oxysterol in CEM cells is associated with negative regulation of c-myc.
Previously we have demonstrated that treatment of the human lymphoblastic leukemic CEM cells with 25-hydroxycholesterol (25OHC) induces apoptosis. In the present study, we show that both c-myc mRNA and c-Myc protein levels are reduced only in oxysterol-sensitive and not in oxysterol-resistant cells after treatment with concentrations of 25OHC that kill the sensitive CEM cells. The repression of c-Myc protein precedes c-myc mRNA reduction, and both events occur before the onset of cell death. Our data suggest that 25OHC-induced suppression of c-myc gene expression in CEM cells results from posttranscriptional regulation. These results demonstrate the regulation by an oxysterol of a gene/gene product important for cell growth and viability and an association between oxysterol-induced apoptosis of CEM cells and the negative regulation of c-myc.
Ayala-Torres
S
S
Department of Human Biological Chemistry & Genetics, University of Texas Medical Branch, Galveston, Texas, 77555-0645, USA.
Zhou
F
F
Thompson
E B
EB
D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D016259:Genes, myc / Q000235:genetics*; D006207:Half-Life; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007945:Leukemia, Lymphoid; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D006888:Hydroxycholesterols; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C007997:25-hydroxycholesterol; D020169:Caspases