Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells.
The effects of dexamethasone, a synthetic glucocorticoid, and of N,N-dimethylformamide on in vitro growth and differentiation and on proto-oncogene expression of human rhabdomyosarcoma cells were studied. RD/18 clone cells (derived from the embryonal rhabdomyosarcoma cell line RD) treated with 100 nM dexamethasone showed an almost complete block of differentiation: about 5% myosin-positive cells were observed after 2 weeks of culture in dexamethasone-supplemented differentiation medium, compared to 20% of untreated cultures. Dexamethasone also induced a 20-30% growth inhibition and a more flattened morphology. The treatment with N,N-dimethylformamide induced a significantly increased proportion of myosin-positive cells (reaching about 30%) and a 40% growth inhibition. Induction of differentiation inversely correlated with the levels of c-myc proto-oncogene expression: after a 2 week culture dexamethasone-treated cells showed the highest c-myc expression and N,N-dimethylformamide-treated cells the lowest. Culture conditions per se down-modulated c-erbB1 and up-regulated c-jun expression, with no relationship to the differentiation pattern. Other proto-oncogenes were not expressed (c-sis, N-myc, c-mos, c-myb) or were not modulated (c-fos, c-raf). Therefore dexamethasone and N,N-dimethylformamide, both causing a decreased growth rate, showed opposing actions on myogenic differentiation and on c-myc proto-oncogene expression of human rhabdomyosarcoma cells.
De Giovanni
C
C
Istituto di Cancerologia, University of Bologna, Italy.
Lollini
P L
PL
Dolcetti
R
R
Landuzzi
L
L
Nicoletti
G
G
D'Andrea
E
E
Scotland
K
K
Nanni
P
P
D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D004126:Dimethylformamide / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000187:drug effects / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D003907:Dexamethasone; D004126:Dimethylformamide