Dexamethasone mediated stabilization of insulin receptor mRNA.
To determine the mechanism of glucocorticoid mediated enhancement of insulin receptor (IR) gene expression, we cotransfected a glucocorticoid receptor expression vector and a plasmid containing a reporter gene driven by an MMTV or IR promoter into COS 7 cells. Dexamethasone (Dex) increased MMTV promoter activity by 100% but had no effect on IR promoter activity. In the glucocorticoid responsive breast cancer cell line, MCF-7, Dex increased IR mRNA by 60%, and increased the IR mRNA half-life from approximately 6hrs to > 24 hrs. No glucocorticoid responsive element could be located in the insulin receptor 3' untranslated region. Glucocorticoids stabilize IR mRNA.
Hines
D
D
Department of Endocrinology, McGuire VAMC, Richmond, VA 23249.
Hug
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V
Levy
J R
JR
D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D012333:RNA, Messenger / Q000187:drug effects*; D011972:Receptor, Insulin / Q000235:genetics*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D003907:Dexamethasone; D011972:Receptor, Insulin