Expression of c-jun protooncogene in human myelomonocytic cells.
A prototypic "immediate early" gene, c-fos, has been extensively investigated in relation to the differentiation and activation of myelomonocytic cells. The c-fos gene product is associated in transcriptional complexes with the c-jun product. These protooncogenes are part of the regulatory network of gene expression. The present study was designed to investigate expression of the c-jun protooncogene in human circulating myelomonocytic cells. We found that c-jun is constitutively expressed in normal monocytes and granulocytes, whereas low levels of transcripts are found in lymphocytes. Acute myelogenous leukemia (AML) samples of French-American-British Cooperative Group (FAB) subtypes 1 through 4 express appreciable levels of this protooncogene. Normal phytohemagglutinin (PHA)-activated lymphocytes express high levels of c-jun. Expression in normal myelomonocytic cells is detectable even after 18 hours of culture. The c-jun transcripts in myelomonocytic cells have a half-life of approximately 20 minutes and are superinduced by cycloheximide, which affects both the degradation rate of mRNA and the transcriptional activity of the c-jun gene. Functional activation of monocytes and granulocytes with phorbol esters, lipopolysaccharide, and tumor necrosis factor (TNF) increase c-jun expression. This induction is rapid, transient, and does not require intervening protein synthesis. Runoff experiments showed that in freshly isolated untreated monocytes, the c-jun gene is constitutively transcribed, and that induction by lipopolysaccharide is at least in part at the transcriptional level. Moreover, lipopolysaccharide (LPS) treatment reduced the degradation rate of c-jun transcripts, prolonging the half-life to approximately two hours. Expression of c-jun in resting and activated monocytes and granulocytes suggests that this protooncogene may play a role in the differentiation and activation of cells belonging to the myelomonocytic lineage.
Bertani
A
A
Instituto di Ricerche Farmacologiche Mario Negri, Milano Italy.
Polentarutti
N
N
Sica
A
A
Rambaldi
A
A
Mantovani
A
A
Colotta
F
F
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D003609:Dactinomycin / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D012313:RNA / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D012313:RNA; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate