Transcriptional regulation of c-jun gene expression by arabinofuranosylcytosine in human myeloid leukemia cells.
Previous studies have demonstrated that 1-beta-D-arabinofuranosylcytosine (ara-C) induces terminal differentiation of human myeloid leukemia cells. Other studies have shown that the c-jun protooncogene is expressed during phorbol ester-induced myeloid differentiation. This work examines the effects of ara-C on c-jun gene expression in human KG-1 myeloid leukemia cells. The results demonstrate that c-jun transcripts are undetectable in uninduced KG-1 cells and that ara-C induces expression of this gene in a concentration- and time-dependent manner. Ara-C treatment was also associated with increases in c-jun transcripts in U-937, THP-1, and HL-60 myeloid leukemia cells. Furthermore, transcriptional run-on analysis has demonstrated that exposure to ara-C increases the rate of c-jun gene transcription. The results also demonstrate that while inhibition of protein synthesis superinduces c-jun mRNA levels in phorbol ester-treated KG-1 cells, cycloheximide had no effect on the induction of c-jun transcripts during ara-C treatment. Moreover, the half-life of c-jun transcripts in ara-C-treated KG-1 cells was 42 min. These findings suggest that the increase in c-jun mRNA observed during ara-C treatment is regulated by a transcriptional mechanism, and that c-jun may be involved in the induction of differentiation and regulation of gene expression by ara-C.
Kharbanda
S M
SM
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Sherman
M L
ML
Kufe
D W
DW
D000199:Actins / Q000235:genetics; D015152:Blotting, Northern; D002453:Cell Cycle; D002454:Cell Differentiation; D003561:Cytarabine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000199:Actins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D003561:Cytarabine; D003609:Dactinomycin; D013755:Tetradecanoylphorbol Acetate