ArticleCell death & disease2012
Glucocorticoid-mediated BIM induction and apoptosis are regulated by Runx2 and c-Jun in leukemia cells.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Associations between Diabetes Mellitus and Selected Cancers.International journal of molecular sciences · 2024Review
- Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells.Blood neoplasia · 2024Article
- Possible Participation of Adenine Nucleotide Translocase ANT1 in the Cytotoxic Action of Progestins, Glucocorticoids, and Diclofenac on Tumor Cells.Pharmaceutics · 2023Article
- JUN mediates glucocorticoid resistance by stabilizing HIF1a in T cell acute lymphoblastic leukemia.iScience · 2023Article
- LRH-1/NR5A2 interacts with the glucocorticoid receptor to regulate glucocorticoid resistance.EMBO reports · 2022Article
- The Relationship Between Diabetes Mellitus and Cancers and Its Underlying Mechanisms.Frontiers in endocrinology · 2022Review
- The long noncoding RNA HOTAIRM1 controlled by AML1 enhances glucocorticoid resistance by activating RHOA/ROCK1 pathway through suppressing ARHGAP18.Cell death & disease · 2021Article
- Article
- Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment.Cancer science · 2021Article
- Comparative efficacy of glucocorticoid receptor agonists on Th2 cell function and attenuation by progesterone.BMC immunology · 2020Article
- Glucocorticoids enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia.Blood · 2020Article
- Integrative genomic analyses reveal mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia.Nature cancer · 2020Article
- Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head.International journal of biological sciences · 2020Article
- IL-2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?Immunity, inflammation and disease · 2019Article
- Influence of BCL2L11 polymorphism on osteonecrosis during treatment of childhood acute lymphoblastic leukemia.The pharmacogenomics journal · 2019Article
- Protective effects of cytokine combinations against the apoptotic activity of glucocorticoids on CD34Cytotechnology · 2019Article
- Glucocorticoids-All-Rounders Tackling the Versatile Players of the Immune System.Frontiers in immunology · 2019Review
- RUNX2 Promotes Malignant Progression in Glioma.Neurochemical research · 2018Article
- Mitochondrial determinants of cancer health disparities.Seminars in cancer biology · 2017Review
- Diagnostic value of the dual-luciferase report assay for predicting response to glucocorticoid in children with acute lymphoblastic leukemia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Glucocorticoids (GCs) are common components of many chemotherapeutic regimens for lymphoid malignancies. GC-induced apoptosis involves an intrinsic mitochondria-dependent pathway. BIM (BCL-2-interacting mediator of cell death), a BCL-2 homology 3-only pro-apoptotic protein, is upregulated by dexamethasone (Dex) treatment in acute lymphoblastic leukemia cells and has an essential role in Dex-induced apoptosis. It has been indicated that Dex-induced BIM is regulated mainly by transcription, however, the molecular mechanisms including responsible transcription factors are unclear. In this study, we found that Dex treatment induced transcription factor Runx2 and c-Jun in parallel with BIM induction. Dex-induced BIM and apoptosis were decreased in cells harboring dominant-negative c-Jun and were increased in cells with c-Jun overexpression. Cells harboring short hairpin RNA for Runx2 also decreased BIM induction and apoptosis. On the Bim promoter, c-Jun bound to and activated the AP-1-binding site at about -2.7 kb from the transcription start site. Treatment with RU486, a GC receptor antagonist, blocked Dex-induced Runx2, c-Jun and BIM induction, as well as apoptosis. Furthermore, pretreatment with SB203580, a p38-mitogen-activated protein kinase (MAPK) inhibitor, decreased Dex-induced Runx2, c-Jun and BIM, suggesting that p38-MAPK activation is upstream of the induction of these molecules. In conclusion, we identified the critical signaling pathway for GC-induced apoptosis, and targeting these molecules may be an alternative approach to overcome GC-resistance in leukemia treatment.
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