Post-transcriptional control of c-myc proto-oncogene expression by glucocorticoid hormones in human T lymphoblastic leukemic cells.
We have studied the regulation of the human c-myc proto-oncogene by glucocorticoid hormones in T lymphoblastic leukemic cells. A significant decrease (50%) of the steady state levels of c-myc mRNA was observed as early as 3 h after dexamethasone treatment of CEM-1.3 human lymphoma cells, reaching less than 5% values, with respect to untreated cells, 24 h after hormone administration. Nuclear run-on experiments showed no modifications of the transcriptional rate from the first exon. However, a slight decrease (15%) of the transcript elongation from the first exon/first intron boundary was observed in the dexamethasone-treated cells. Using actinomycin D to block gene transcription, we have observed a significant increase in the rate of c-myc RNA specific decay after dexamethasone treatment. Furthermore, cycloheximide was able to overcome completely the dexamethasone-induced down-regulation of the c-myc gene expression. Our data suggest that dexamethasone is able to inhibit human c-myc gene expression primarily at the post-transcriptional level, through the synthesis of hormone-induced regulatory protein(s) controlling c-myc transcript stability.
Maroder
M
M
Department of Experimental Medicine, University La Sapienza, Roma, Italy.
Martinotti
S
S
Vacca
A
A
Screpanti
I
I
Petrangeli
E
E
Frati
L
L
Gulino
A
A
D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D003907:Dexamethasone; D003513:Cycloheximide