Induction of c-fos gene expression by arabinofuranosylcytosine in human KG-1 leukemia cells.
Previous studies have demonstrated that the c-fos proto-oncogene is expressed during induction of differentiation and as an immediate early response to growth factors. The present results demonstrate that exposure of human KG-1 myeloid leukemic cells to 1-beta-D-arabinofuranosylcytosine (ara-C) was associated with increases in c-fos gene expression. This effect was dependent on the concentration and time of ara-C treatment. The level of c-fos transcripts was maximal after 6 hr of exposure to 5 x 10(-6) M ara-C and subsequently declined to that in untreated cells. Nuclear run-on assays demonstrated low to undetectable levels of c-fos gene transcription in untreated KG-1 cells. In contrast, treatment with 5 x 10(-6) M ara-C for 6 hr was associated with increases in transcription of this gene. Although superinduction of c-fos expression has been observed at the post-transcriptional level in the presence of protein synthesis inhibition, this effect was not detectable in ara-C-treated KG-1 cells. These combined results demonstrate that ara-C increased c-fos mRNA levels in KG-1 cells and that this effect was associated with transcriptional activation of the c-fos gene.
Kharbanda
S
S
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Datta
R
R
Kufe
D
D
D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D003561:Cytarabine; D003609:Dactinomycin; D003513:Cycloheximide