Induction of c-jun expression in the myeloid leukemia cell line KG-1 by 1-beta-D-arabinofuranosylcytosine.
c-Jun/AP-1 is a transcription factor commonly induced in mammalian cells by serum, phorbol compounds, or peptide growth factors. We show that c-Jun/AP-1 is inducible as well as coordinately regulated, in the human acute myelogenous leukemia cell line KG-1, by the cytostatic drug 1-beta-D-arabinofuranosylcytosine (Ara-C). Concomitantly with Ara-C treatment, growth inhibition and loss of clonogenic survival of KG-1 cells were observed. Whereas KG-1 cells displayed only barely detectable amounts of c-jun transcripts when cultured in the presence of serum, Ara-C at concentrations of 1 to 50 microM induced c-jun transcripts in a dose-dependent fashion. Time course studies showed that 10 microM Ara-C induced c-jun transcripts 6 hr after initiation of culture. Induction of c-jun mRNA was independent of de novo protein synthesis, because the protein synthesis inhibitor cycloheximide failed to alter Ara-C-induced c-jun mRNA accumulation. Furthermore, cycloheximide did not induce c-jun transcripts, ruling out the possibility of posttranscriptional stabilization of c-jun mRNA by labile proteins, as has been previously reported for a variety of serum-inducible protooncogenes and early response genes. Moreover, nuclear run-on analysis disclosed that c-jun induction by Ara-C in KG-1 cells took place at a transcriptional level. Taken together, these findings indicate that c-jun mRNA, unlike its rapid (within minutes) induction by serum in fibroblasts, is induced by Ara-C in KG-1 cells following a much more prolonged time course and is regulated essentially at a transcriptional level.
Henschler
R
R
Department of Hematology and Oncology, University of Freiburg Medical Center, Federal Republic of Germany.
Brennscheidt
U
U
Mertelsmann
R
R
Herrmann
F
F
D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D014176:Protein Biosynthesis; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D003561:Cytarabine; D003513:Cycloheximide