Glucocorticoid regulation of thymidine kinase (Tk-1) expression in L929 cells.
Glucocorticoids regulate the proliferation of mouse L cells. Incorporation of [3H]thymidine is inhibited by 70-90% within 24 h after addition of 0.1 microM dexamethasone. This effect on L cells is completely reversible. The expression of the thymidine kinase gene (Tk-1) has been examined in L cells that have been treated with 0.1 microM dexamethasone for 24 h. Dexamethasone inhibits thymidine kinase activity 70-90% after 24 h. This is associated with a 90-95% decrease in Tk mRNA abundance. The decrease in Tk mRNA is not caused by a decrease in transcription of Tk-1, as shown by nuclear run-on transcription assays. Transient expression of the CAT (chloramphenicol acetyltransferase) gene, driven by the Tk-1 promoter, was not affected by dexamethasone, and transcription of stably integrated Tk minigenes in LMTk- cells was not affected by dexamethasone. This effect was observed regardless of whether Tk cDNA was fused to the simian virus 40 promoter or the mouse Tk-1 promoter region. Conversely, expression of thymidine kinase was inhibited when stable Tk+ transformants of LMTk- cells were exposed to glucocorticoids; and inhibition of expression was observed irrespective of the promoter that was used to drive transcription of the Tk minigenes. These data indicate that glucocorticoid regulation of Tk-1 in mouse L cells is, within the limits of detection of the assays used in these studies, entirely due to a posttranscriptional mechanism.
Frost
G H
GH
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Rhee
K
K
Thompson
E A
EA
D000818:Animals; D015152:Blotting, Northern; D002678:Chimera; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000502:physiology*; D007739:L Cells; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014170:Transformation, Genetic
D005938:Glucocorticoids; D012333:RNA, Messenger; D015735:Mifepristone; D003907:Dexamethasone; D013937:Thymidine Kinase