Activation of the transcription factor kappa B in human KG-1 myeloid leukemia cells treated with 1-beta-D-arabinofuranosylcytosine.
The present studies have examined the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) on activation of the transcription factor kappa B (NF-kappa B). The results demonstrate that treatment of human KG-1 myeloid leukemia cells with ara-C is associated with induction of protein binding to the NF-kappa B consensus sequence. NF-kappa B binding was activated at 30 min and reached maximal levels of binding at 1-2 hr of ara-C treatment. The NF-kappa B consensus sequence was ligated to the heterologous thymidine kinase (TK) promoter and the human growth hormone (GH) reporter gene to determine whether ara-C-induced NF-kappa B activity includes an enhancer function. Ara-C treatment had little effect on transient expression of pTKGH in KG-1 cells but increased transcription of the p (NF-kappa B) TKGH vector by 8-fold. The results also demonstrate that ara-C transiently increases NF-kappa B mRNA levels. However, the finding that ara-C-induced binding of NF-kappa B to DNA occurs in the presence of cycloheximide indicates that this agent activates preexisting NF-kappa B protein. These results suggest that ara-C induces a cytoplasmic pathway that transduces signals to the nucleus by activation of NF-kappa B.
Brach
M A
MA
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Kharbanda
S M
SM
Herrmann
F
F
Kufe
D W
DW
D001483:Base Sequence; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004586:Electrophoresis; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014178:Translocation, Genetic / Q000502:physiology; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D009687:Nuclear Proteins; D003561:Cytarabine; D004247:DNA