title: Glucocorticoid effect on oncogene/growth gene expression in human T lymphoblastic leukemic cell line CCRF-CEM. Specific c-myc mRNA suppression by dexamethasone.
abstract: 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.
authors.affiliation: Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
authors.forename: Y S
authors.initials: YS
authors.lastname: Yuh
authors.forename: E B
authors.initials: EB
authors.lastname: Thompson
mesh_terms: 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*
chemical_list: D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003907:Dexamethasone