1907849

pubmed:Citation

32

1-beta-D-Arabinofuranosylcytosine (ara-C) is an effective chemotherapeutic agent that incorporates into DNA and results in DNA fragmentation. Recent work has demonstrated that ara-C transiently induces expression of the c-jun immediate early response gene. The present studies in HL-60 myeloid leukemia cells extend these findings by demonstrating that the increase in c-jun mRNA levels at 6 h of ara-C treatment is regulated by a transcriptional mechanism. In contrast, the subsequent down-regulation of c-jun expression is controlled by a posttranscriptional decrease in the stability of the c-jun transcripts. Previous work in phorbol ester treated cells has indicated that c-jun expression is regulated by the activation of protein kinase C. The present results demonstrate that protein kinase C activity is increased in ara-C-treated cells. This increase was maximal at 60 min and remained detectable through 6 h of ara-C exposure. Moreover, the induction of c-jun transcripts by ara-C was inhibited by the isoquinolinesulfonamide derivative H7, but not by HA1004, suggesting that this effect is mediated by protein kinase C. Ara-C-induced c-jun expression was also inhibited by staurosporine, another inhibitor of protein kinase C. Taken together, these results indicate that the cellular response to ara-C includes the activation of protein kinase C and that ara-C potentially induces c-jun transcription by a protein kinase C dependent signaling mechanism.

eng

IM

MEDLINE

0006-2960

Print

30

NLM

7947-52

pubmed-meshheading:1907849-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, pubmed-meshheading:1907849-Aphidicolin, pubmed-meshheading:1907849-Cell Line, pubmed-meshheading:1907849-Cell Nucleus, pubmed-meshheading:1907849-Cycloheximide, pubmed-meshheading:1907849-Cytarabine, pubmed-meshheading:1907849-DNA-Binding Proteins, pubmed-meshheading:1907849-Dactinomycin, pubmed-meshheading:1907849-Diterpenes, pubmed-meshheading:1907849-Enzyme Activation, pubmed-meshheading:1907849-Gene Expression Regulation, Neoplastic, pubmed-meshheading:1907849-Humans, pubmed-meshheading:1907849-Isoquinolines, pubmed-meshheading:1907849-Kinetics, pubmed-meshheading:1907849-Leukemia, Promyelocytic, Acute, pubmed-meshheading:1907849-Piperazines, pubmed-meshheading:1907849-Protein Kinase C, pubmed-meshheading:1907849-Protein-Tyrosine Kinases, pubmed-meshheading:1907849-Proto-Oncogene Proteins c-jun, pubmed-meshheading:1907849-Proto-Oncogenes, pubmed-meshheading:1907849-RNA, Neoplasm, pubmed-meshheading:1907849-Sulfonamides, pubmed-meshheading:1907849-Transcription, Genetic, pubmed-meshheading:1907849-Transcription Factors

Regulation of c-jun gene expression in HL-60 leukemia cells by 1-beta-D-arabinofuranosylcytosine. Potential involvement of a protein kinase C dependent mechanism.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't