Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation

The differentiation into macrophages of the monocytic cell line U-937 or the monomyelocytic cell line HL-60 induced by phorbol esters is accompanied by a rapid induction of the expression of the proto-oncogene c- fos. Maximal levels of c- fos gene transcripts accumulate within 20–30 min following induction. By 2 hr, the c- fos-specific mRNA level drops 5 to 10 fold below that detected at 30 min after induction. The concentration of c- fos mRNA remains unchanged for the next 5 days, at which time over 99% of the viable precursor cells are converted to adherent macrophages. c- fos protein can be detected within 20 min of induction, reaching maximal levels by 40–60 min. Little or no c- fos protein is detected by 120–150 min after induction, even though c- fos mRNA remains detectable. Presence of cycloheximide leads to superinduction of c- fos mRNA transcripts. No c- fos gene transcripts are detected when the HL-60 cell line is induced with Me2SO to differentiate to granulocytes. A role for the c- fos protein is envisaged in the monocyte differentiation pathway.