Abstract |
The mode of action of the differentiation inducer 1-beta-D-arabinofuranosylcytosine ( ara-C) is as yet unknown. We have analyzed the role of c-myc expression in ara-C-induced differentiation of K562 human erythroleukemia cells. Six hours after differentiation induction, c-myc expression is down-regulated transiently. This was followed by the onset of cell differentiation together with a final c-myc 'down-regulation' at 24 h after treatment. This regulation of expression may be caused by hypermethylation of c-myc DNA sequences, which we find to follow a similar pattern. We propose that the loss of c-myc expression might be a necessary prerequisite for ara-C-induced differentiation. This hypothesis was tested by transfecting a constitutive c-myc expression construct into K562 cells prior to ara-C treatment. By following the differentiation parameters cell morphology, benzidine staining ( hemoglobin monitored), and alkaline phosphatase activity (presence of mature red blood cell antigen monitored) in cells expressing cotransfected LacZ marker gene, it was demonstrated that the introduction of the c-myc expression plasmid blocked ara-C-induced differentiation. We conclude that loss of c-myc expression mediated the differentiation found in ara-C-treated K562 cells.
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Authors | S J Baker, M Pawlita, A Leutz, D Hoelzer |
Journal | Leukemia
(Leukemia)
Vol. 8
Issue 8
Pg. 1309-17
(Aug 1994)
ISSN: 0887-6924 [Print] England |
PMID | 8057666
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hemoglobins
- Proto-Oncogene Proteins c-myc
- Cytarabine
- Chloramphenicol O-Acetyltransferase
- beta-Galactosidase
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Topics |
- Blotting, Northern
- Cell Differentiation
(drug effects, physiology)
- Cell Line
- Chloramphenicol O-Acetyltransferase
(biosynthesis)
- Cytarabine
(pharmacology)
- Erythrocytes
(cytology, metabolism)
- Gene Expression
(drug effects)
- Genes, myc
- Hemoglobins
(biosynthesis)
- Humans
- Kinetics
- Leukemia, Erythroblastic, Acute
- Proto-Oncogene Proteins c-myc
(biosynthesis)
- Time Factors
- Transfection
- Tumor Cells, Cultured
- beta-Galactosidase
(biosynthesis)
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