K562 leukemia cells transfected with the human c-fes gene acquire the ability to undergo myeloid differentiation.
Expression of the proto-oncogene p93c-fes and its associated tyrosine kinase activity is marked in mature granulocytes, monocytes, differentiated HL-60 leukemia cells, and leukemia cell lines KG-1, THP-1, HEL, and U-937, which can be induced to differentiate along the granulocyte/monocyte pathway. Conversely, p93-c-fes expression is absent in the K562 cell line, which is resistant to myeloid differentiation. Upon transfection and clonal selection of K562 cells using a mammalian expression vector containing the 13-kilobase pair c-fes gene, c-fes mRNA was transcribed and p93-c-fes tyrosine activity kinase was expressed. Clones expressing c-fes underwent myeloid differentiation as assessed by the appearance of phagocytic activity, Fc receptors, nitro blue tetrazolium reduction, Mac-1 immunofluorescence, and lysozyme production. These results indicate that the expression of the c-fes protooncogene and its associated tyrosine kinase activity plays a major role in the initiation of myeloid differentiation.
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Laboratory of Biological Chemistry, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892.
Smithgall
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Glazer
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D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D005822:Genetic Vectors; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051578:Proto-Oncogene Proteins c-fes; D011519:Proto-Oncogenes; D014162:Transfection
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496645:FES protein, human; D051578:Proto-Oncogene Proteins c-fes