Coordinate Regulation of Glucocorticoid Receptor and c-jun Gene Expression Is Cell Type-Specific and Exhibits Differential Hormonal Sensitivity for Down- and Up-Regulation
| Autor: | Wayne V. Vedeckis, Eva Vig, Thomas J. Barrett |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Time Factors
Transcription Genetic Proto-Oncogene Proteins c-jun Down-Regulation Tretinoin Biology Triamcinolone Acetonide Biochemistry Cell Line Mice L Cells Receptors Glucocorticoid Glucocorticoid receptor Transcription (biology) Gene expression Tumor Cells Cultured Animals Homeostasis Pituitary Neoplasms RNA Messenger Transcription factor Messenger RNA c-jun Precursor Cell Lymphoblastic Leukemia-Lymphoma Molecular biology Up-Regulation Kinetics Gene Expression Regulation Apoptosis Cell culture |
| Zdroj: | Biochemistry. 35:9746-9753 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi960058j |
| Popis: | We have previously proposed a novel mechanism for the coupled regulation of glucocorticoid receptor (GR) and c-jun transcription in triamcinolone acetonide (TA)-treated AtT-20 cells. This involved transcriptional interference of AP-1 (Fos/Jun)-driven gene transcription by the formation of inactive GR/Jun heterodimers. To further elucidate the molecular mechanism for GR autoregulation, the expression of GR and c-jun mRNA and protein levels were examined in both mouse L929 fibroblast cells and human CEM-C7 acute lymphoblastic leukemia cells. A rapid down-regulation of both GR and c-jun mRNA and protein levels occurs in TA-treated L929 cells. All-trans-retinoic acid (RA) treatment of Jun-deficient, mouse F9, teratocarcinoma cells causes the induction of c-jun expression. The increased expression of both c-jun mRNA and protein is accompanied by the induction of GR expression. These data further suggest that functional cJun is needed for the expression of the GR and c-jun genes in F9 cells. CEM-C7 cells undergo apoptosis after exposure to glucocorticoids. There is a parallel up-regulation of GR and c-jun mRNA levels in TA-treated CEM-C7 cells. This is accompanied by a concomitant increase in GR and cJun protein levels. Dose-response analyses reveal the expected coordinate regulation of both GR and c-jun mRNA and protein in L929 cells (decreasing) and in CEM-C7 cells (increasing). However, approximately 20-fold less TA is required for the inhibition of GR and c-jun expression as compared to that required for the stimulation of these two genes. These data demonstrate that the coordinate regulation of GR and c-jun gene expression is dose-dependent and cell type-specific. These results, along with previously reported data, suggest that GR complex formation with itself or with another transcription factor is important for the coordinate up- and down-regulation, respectively, of the GR and c-jun genes. |
| Databáze: | OpenAIRE |
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