title: Regulation of jun-B gene expression by 1-beta-D-arabinofuranosyl-cytosine in human myeloid leukemia cells.
abstract: The jun-B gene is a member of the jun family of immediate early response genes that regulate cellular responses to growth factors. The present studies have examined the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) on jun-B expression in human KG-1 myeloid leukemia cells. The results demonstrate that ara-C increases jun-B mRNA levels. The level of jun-B transcripts was maximal after 12 hr of exposure to 10(-5) M ara-C and persisted through 72 hr. Nuclear run-on assays demonstrated that ara-C treatment is associated with an increased rate of jun-B gene transcription. The results also demonstrate that ara-C-induced jun-B mRNA levels are regulated by a posttranscriptional mechanism. The level of jun-B transcripts in ara-C-treated cells was superinduced by inhibition of protein synthesis. Moreover, cycloheximide prolonged the half-life of ara-C-induced jun-B transcripts. These results, thus, demonstrate that ara-C induces expression of the jun-B gene in KG-1 cells and that this effect is mediated by transcriptional and posttranscriptional mechanisms.
authors.affiliation: Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: R
authors.initials: R
authors.lastname: Datta
authors.forename: S
authors.initials: S
authors.lastname: Kharbanda
authors.forename: D
authors.initials: D
authors.lastname: Kufe
mesh_terms: D003513:Cycloheximide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D016759:Oncogene Protein p65(gag-jun); D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D016759:Oncogene Protein p65(gag-jun); D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D015682:Retroviridae Proteins, Oncogenic; D003561:Cytarabine; D003513:Cycloheximide