Cytotoxic effect of TNF-alpha and abnormal regulation of cAMP in the retinoid resistant cell line U937/GTB.
We have studied the effect of retinoids, forskolin and TNF-alpha on two sublines of U937 cells, U937/clone 4 and U937/GTB. Retinoids induced differentiation of U937/clone 4, while the U937/GTB cells were resistant to induction of differentiation by retinoids. Retinoids effectively reduced the proliferation of both U937/clone 4 and U937/GTB, and decreased the steady state levels of c-myc mRNA in both sublines. Furthermore, the retinoid resistant U937/GTB cells were hypersensitive to the cytotoxic effect of TNF-alpha. Forskolin increased the cAMP level in the U937/clone 4 cells 14 times above basal level, but did not change the cAMP concentration in the U937/GTB cells.
Botilsrud
M
M
Institute for Nutrition Research, School of Medicine, University of Oslo, Norway.
Kvam
L
L
Blomhoff
H K
HK
Norum
K R
KR
Blomhoff
R
R
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004351:Drug Resistance; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology*; D009857:Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014801:Vitamin A; D005576:Colforsin; D014212:Tretinoin; D000242:Cyclic AMP