Glucocorticoid effect on oncogene/growth gene expression in human T lymphoblastic leukemic cell line CCRF-CEM. Specific c-myc mRNA suppression by dexamethasone.
Glucocorticoids induce growth inhibition and eventually cause cell lysis in certain sensitive leukemic cells. To investigate how glucocorticoids interact with cell growth pathways, we studied the expression of 14 growth-related genes in dexamethasone-treated CEM-C7A cells, a steroid-sensitive clone of the CCRF-CEM cell line, and in several closely related clones. The 14 genes studied were chosen to represent four different levels of mitogenic signal transduction. Detectable mRNA levels were found for 8 of the 14 genes, but among these only c-myc expression was obviously suppressed by dexamethasone. The c-myc mRNA levels declined abruptly during the first 12 h after addition of 1 microM dexamethasone, and maximal suppression occurred by 18 h. This change was not seen in the C7A controls, in the glucocorticoid-resistant, receptor-deficient clone ICR-27, or in the glucocorticoid-resistant, receptor-positive clone C1. H.10, a hybrid clone between C1 and ICR-27, showed restoration of the sensitive phenotype, and in H.10 cells the c-myc mRNA was also suppressed by dexamethasone. Our results suggest that: 1) functional glucocorticoid receptor is required for inducing c-myc suppression. 2) In dexamethasone-resistant cells with functional receptors c-myc is not suppressed. 3) The growth arrest induced by glucocorticoids correlates with, and may be regulated via, suppression of c-myc expression.
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Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Thompson
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D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D007700:Kinetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics; D009693:Nucleic Acid Hybridization; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects*
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003907:Dexamethasone