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Glucocorticoids inhibit apoptosis during fibrosarcoma development by transcriptionally activating Bcl-x(L)

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Date
2003-05-16
ICR Author
Vivanco, Maria
Author
Gascoyne, DM
Kypta, RM
Vivanco, MDM
Type
Journal Article
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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.
URI
https://repository.icr.ac.uk/handle/internal/2679
DOI
https://doi.org/10.1074/jbc.M301812200
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Language
eng
License start date
2003-05-16
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 pp. 18022 - 18029
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

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