Regulation of c-fgr messenger RNA levels in U937 cells treated with different modulating agents.

The U937 cell line was used to investigate the induction of messenger RNA (mRNA) for the c-fgr mRNA tyrosine kinase proto-oncogene in cells of the monocyte-macrophage lineage. U937 cells were exposed to tumour necrosis factor-alpha (TNF-alpha), TNF-beta and transforming growth factor-alpha (TGF-alpha), alone and in combination with PMA and 1,25-dihydroxycholecalciferol (1,25-DHCC). TNF-alpha and TNF-beta, but not TGF-alpha, decreased the proliferation of U937 cells in a time- and dose-dependent manner, and both TNF-alpha and TNF-beta enhanced the response of U937 cells to PMA during the first 24 hr of treatment and to 1,25-DHCC over 72 hr. TNF-alpha induced a rapid increase in c-fgr mRNA levels within 4 hr, in contrast to slower induction by PMA and 1,25-DHCC. TNF-alpha and 1,25-DHCC together had an additive effect on c-fgr mRNA levels. In U937 cells exposed to PMA, c-fgr mRNA levels continued to increase over 72 hr. Levels of c-fgr mRNA induced by the various modulating agents did not correlate clearly with the changes in proliferation. Therefore, we suggest that although the c-fgr gene product may have a role in differentiation, the more significant role is likely to be in the fully differentiated macrophage.