Differentiation of WEHI-3B D+ myelomonocytic leukemia cells induced by ectopic expression of the protooncogene c-jun.
The product of the protooncogene c-jun is one of the components of the AP-1 transcription factor complex, which is involved in the control of cell proliferation and differentiation. To study the role of c-jun in leukemia cell growth and maturation, a plasmid (pMTJ11) was constructed that contained the rat c-jun complementary DNA under the control of the human metallothionein promoter and the neo gene. Murine myelomonocytic WEHI-3B D+ cells were transfected by electroporation with the linearized pMTJ11 plasmid and subsequently cloned in the presence of G-418. Exposure of these clones to cadmium resulted in a high level of expression of c-jun mRNA and protein, as demonstrated by Northern hybridization and Western blotting. When these clones were examined immediately after their establishment, expression of c-jun was accompanied by the appearance of a mature phenotype in many clones, as measured by the reduction of nitroblue tetrazolium and by the expression of Mac-1 (CD11b), a cell surface marker on differentiated cells. Morphological changes indicative of the differentiated state were also observed by staining. These findings indicate that expression of c-jun is capable of initiating the differentiation of WEHI-3B D+ cells in the absence of an external inducer of maturation. Furthermore, the expression of c-jun led to an enhancement of the induction of the differentiation of WEHI-3B D+ cells by retinoic acid, suggesting an involvement of c-jun in the retinoic acid signal transduction pathway.
Li
J
J
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
King
I
I
Sartorelli
A C
AC
D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D002104:Cadmium / Q000494:pharmacology; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic; D016758:Genes, jun; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008666:Metalloendopeptidases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
D015415:Biomarkers; D016177:Macrophage-1 Antigen; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D002104:Cadmium; D014212:Tretinoin; D008666:Metalloendopeptidases