title: Coordinate regulation of glucocorticoid receptor and c-jun gene expression is cell type-specific and exhibits differential hormonal sensitivity for down- and up-regulation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Barrett
authors.forename: E
authors.initials: E
authors.lastname: Vig
authors.forename: W V
authors.initials: WV
authors.lastname: Vedeckis
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis; D007700:Kinetics; D007739:L Cells; D051379:Mice; D010911:Pituitary Neoplasms; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014222:Triamcinolone Acetonide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014212:Tretinoin; D014222:Triamcinolone Acetonide