The fgr protooncogene product is a cytoplasmic tyrosine kinase of the scr family. Its function is unknown, although expression of the protooncogene increases with monocytic differentiation. Due to its structural similarity to other signal transduction proteins such as scr, the fgr product has been postulated to be a signal transducer for monocytic differentiation. To determine if fgr expression is necessary for monocytic differentiation, the promyelocytic human leukemic cell line HL60 is being studied. These biopotent cells are being monocytically induced using each of three known chemical inducers: vitamin D3, the phorbol ester TPA, and phospholipase C. Retinoic acid which induces granulocytic differentiation is being used as a control. Anti-sense oligonucleotides to fgr are being added to the culture medium of HL60 cells, with and without chemical inducers of differentiation. Sense and nonsense fgr oligonucleotides are being used as negative controls. If monocytic differentiation induced by chemical agents requires fgr expression, anti-sense oligonucleotide would be expected to inhibit differentiation. Differentiation is being assayed by expression of non-specific esterase and CD14 cell surface antigens. fgr mRNA is being assayed by reverse transcription polymerase chain reaction amplification.
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