Datta R, Kharbanda S, Kufe D
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Mol Pharmacol. 1990 Oct;38(4):435-9.
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.
