Expression of c-jun during macrophage differentiation of HL-60 cells.
Cellular transcription factors are important in the regulation of cellular genes. Recent studies have indicated that a class of cellular genes known as early response genes are important in the control of cellular growth properties. Two of these genes, c-jun and c-fos, play an important role in the control of cellular differentiation. Because the acute myelogenous leukemia cell line, HL-60, is capable of differentiating to either macrophages or granulocytes, it provides a good model to understand differential gene expression. To determine if the modulation of c-jun was important in the differentiation of HL-60 cells to either macrophages or granulocytes, expression of c-jun mRNA was determined by Northern analysis at various times following treatment with a variety of differentiating agents, including 12-tetradeconyl-phorbol 13-acetate (TPA), retinoic acid (RA), dimethyl sulfoxide (DMSO), or 1,25 dihydroxyvitamin D3 [1,25 (OH)2 D3]. Both TPA and 1,25(OH)2D3, which induce HL-60 cells to differentiate to macrophages, resulted in marked increases in c-jun mRNA; while RA and DMSO, which induce HL-60 cells to differentiate to granulocytes, did not greatly alter c-jun mRNA expression. HL-60 cell lines resistant to macrophage differentiation after exposure to either 1,25(OH)2D3 or TPA did not result in increases in c-jun mRNA. These results suggest that elevation of c-jun mRNA in HL-60 cells correlated temporally with differentiation to macrophages. Thus, c-jun may be a critical cellular transcription factor involved in macrophage differentiation.
Gaynor
R
R
Division of Hematology-Oncology, UCLA School of Medicine, Wadsworth Veterans Hospital.
Simon
K
K
Koeffler
P
P
D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D014212:Tretinoin; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate