Overexpression of the c-fos gene perturbs functional maturation of M1 cells into macrophages.

Expression of the proto-oncogene c-fos is induced in normal myelopoiesis. However, functions of c-Fos in the process of differentiation towards macrophages are still controversial. To explore the functions, we used the murine myeloblastic leukemia cell line M1. Stimulation of M1 cells with bacterial LPS promotes their terminal differentiation into functional macrophages. Overexpression of c-fos in M1 cells dramatically increased sensitivity of the cells for LPS-induced differentiation and generation of morphologically differentiated cells. However, the overexpression did not modulate phagocytotic functions, surface expression of macrophage markers such as CD16/CD32 (Fcgamma Receptor) and CD54 (ICAM-1), and expression of lysozyme, esterase and c-fms mRNA. Surprisingly, induction of the MHC class II expression on M1 cells after stimulation was inhibited by the overexpression. Expression of CIITA, as an essential transcription factor for the expression, was also reduced in the M1 cells. These results suggest that overexpression of c-fos in differentiating M1 cells perturbs their functional maturation.