Acceleration of apoptosis in transforming growth factor beta 1-treated M1 cells ectopically expressing B-myb.
Inappropriate expression of genes involved in cell proliferation can result in altered regulation of apoptosis, a process of programmed cell death. Since B-myb has recently been implicated in the cell cycle progression we wanted to examine its role in the apoptotic process. For this purpose we used transforming growth factor beta 1 (TGF-beta 1)-treated M1 myeloid leukemia cell lines that continuously express murine B-myb. It was found that in cells overexpressing B-myb, TGF-beta 1-induced apoptosis was accelerated as assessed by cell viability and DNA fragmentation into nucleosomal fragments. A DNA ladder was detected after 24 h of TGF-beta 1 treatment in these cells, whereas it was not detected until after 36 h in the parental M1 cells. It was further determined by Northern blot analysis that this higher sensitivity of B-myb overexpressing clones was not due to a change in the expression of TGF-beta receptor type I or in the kinetics of the regulation of c-myc, c-myb, bcl-2, and/or bax.
Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892.
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D016259:Genes, myc; D007951:Leukemia, Myeloid; D051379:Mice; D009707:Nucleosomes / Q000187:drug effects; D009857:Oncogenes; D014176:Protein Biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D012190:Retroviridae; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C499306:Mybl2 protein, mouse; D009707:Nucleosomes; D018125:Receptors, Transforming Growth Factor beta; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta