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.
Faulkner
L
L
Department of Biochemistry and Molecular Biology, Bland Sutton Institute, University College of Middlesex School of Medicine, London, U.K.
Patel
M
M
Brickell
P M
PM
Katz
D R
DR
D000818:Animals; D002117:Calcitriol / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D008233:Lymphotoxin-alpha / Q000502:physiology; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019061:src-Family Kinases
D008233:Lymphotoxin-alpha; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate