C-Jun is Induced to High Continuous Expression During Differentiation of Hematopoietic Cells and is Regulated...

The c-jun proto-oncogene is usually expressed at a low level in most cell types but is induced rapidly and transiently in response to stimuli. The present results show that stimulation of U-937 cells to macrophage differentiation by a phorbol ester or vitamin D3 induced a continuous high level expression of c-jun mRNA and protein. High level expression of c-jun mRNA was also observed in various other human differentiated hematopoietic cells, represented by normal macrophages, HL-60 promyelocytic cells differentiated towards macrophages or granulocytes and in myeloma, but not in immature cell lines. These results might suggest a role of c-jun in the differentiation of several hematopoietic lineages. In U-937, a differential regulation of c-jun and c-fos was demonstrated both with respect to kinetics and to the level of regulation. Furthermore, in subclones of U-937, where maturation and growth arrest could be separated, c-jun was induced in the absence of c-fos and vice versa. Expression of c-jun and c-fos mRNA correlated with maturation and growth arrest, respectively, in these clones. cAMP generating agents, which induced c-jun and c-fos, did, however, not induce terminal differentiation, indicating that other signals, e.g. those associated with down-regulation of c-myb and c-myc, are also required.