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Glucocorticoids inhibit apoptosis during fibrosarcoma development by transcriptionally activating Bcl-xL.
J Biol Chem. 2003 May 16; 278(20):18022-9.JB

Abstract

Glucocorticoids influence many physiological processes, and in particular apoptosis, often with opposite effects depending on the cell type examined. We found that during fibrosarcoma development there is a strong increase in apoptosis at the tumor stage, which is repressed by dexamethasone to levels observed in normal fibroblasts. The anti-apoptotic Bcl-2 family protein Bcl-x(L) is induced by dexamethasone at the transcriptional level at all stages of fibrosarcoma development. The ligand-activated glucocorticoid receptor (GR) activates the Bcl-x promoter in transient transfection experiments, and GR binds to specific Bcl-x promoter sequences in vitro and in vivo. Furthermore, a GR antagonist abolishes this effect, indicating that Bcl-x(L) induction is mediated by GR. Importantly, exogenous Bcl-x(L) inhibits apoptosis and caspase-3 activity in fibrosarcoma cells to levels found in dexamethasone-treated fibrosarcoma cells. We conclude that Bcl-x(L) is a key target mediating the anti-apoptotic effects of glucocorticoids during fibrosarcoma development. These observations provide further understanding of the molecular basis of glucocorticoid regulation of cell death during tumorigenesis.

Authors+Show Affiliations

Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12637494

Citation

Gascoyne, Duncan M., et al. "Glucocorticoids Inhibit Apoptosis During Fibrosarcoma Development By Transcriptionally Activating Bcl-xL." The Journal of Biological Chemistry, vol. 278, no. 20, 2003, pp. 18022-9.
Gascoyne DM, Kypta RM, Vivanco Md. Glucocorticoids inhibit apoptosis during fibrosarcoma development by transcriptionally activating Bcl-xL. J Biol Chem. 2003;278(20):18022-9.
Gascoyne, D. M., Kypta, R. M., & Vivanco, M. d. (2003). Glucocorticoids inhibit apoptosis during fibrosarcoma development by transcriptionally activating Bcl-xL. The Journal of Biological Chemistry, 278(20), 18022-9.
Gascoyne DM, Kypta RM, Vivanco Md. Glucocorticoids Inhibit Apoptosis During Fibrosarcoma Development By Transcriptionally Activating Bcl-xL. J Biol Chem. 2003 May 16;278(20):18022-9. PubMed PMID: 12637494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glucocorticoids inhibit apoptosis during fibrosarcoma development by transcriptionally activating Bcl-xL. AU - Gascoyne,Duncan M, AU - Kypta,Robert M, AU - Vivanco,Maria d M, Y1 - 2003/03/12/ PY - 2003/3/15/pubmed PY - 2003/6/26/medline PY - 2003/3/15/entrez SP - 18022 EP - 9 JF - The Journal of biological chemistry JO - J Biol Chem VL - 278 IS - 20 N2 - Glucocorticoids influence many physiological processes, and in particular apoptosis, often with opposite effects depending on the cell type examined. We found that during fibrosarcoma development there is a strong increase in apoptosis at the tumor stage, which is repressed by dexamethasone to levels observed in normal fibroblasts. The anti-apoptotic Bcl-2 family protein Bcl-x(L) is induced by dexamethasone at the transcriptional level at all stages of fibrosarcoma development. The ligand-activated glucocorticoid receptor (GR) activates the Bcl-x promoter in transient transfection experiments, and GR binds to specific Bcl-x promoter sequences in vitro and in vivo. Furthermore, a GR antagonist abolishes this effect, indicating that Bcl-x(L) induction is mediated by GR. Importantly, exogenous Bcl-x(L) inhibits apoptosis and caspase-3 activity in fibrosarcoma cells to levels found in dexamethasone-treated fibrosarcoma cells. We conclude that Bcl-x(L) is a key target mediating the anti-apoptotic effects of glucocorticoids during fibrosarcoma development. These observations provide further understanding of the molecular basis of glucocorticoid regulation of cell death during tumorigenesis. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12637494/Glucocorticoids_inhibit_apoptosis_during_fibrosarcoma_development_by_transcriptionally_activating_Bcl_xL_ DB - PRIME DP - Unbound Medicine ER -