| PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis. | |
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MedLine Citation:
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PMID: 20435142 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucocorticoids (GCs) cause cell cycle arrest and apoptosis in lymphoid cells which is exploited to treat lymphoid malignancies. The mechanisms of these anti-leukemic GC effects are, however, poorly understood. We previously defined a list of GC-regulated genes by expression profiling in children with acute lymphoblastic leukemia (ALL) during systemic GC monotherapy and in experimental systems of GC-induced apoptosis. PLZF/ZBTB16, a transcriptional repressor, was one of the most promising candidates derived from this screen. To investigate its role in the anti-leukemic GC effects, we performed overexpression and knock-down experiments in CCRF-CEM childhood ALL cells. Transgenic PLZF/ZBTB16 alone had no detectable effect on cell proliferation or survival, but reduced sensitivity to GC-induced apoptosis but not apoptosis induced by antibodies against Fas/CD95 or 3 different chemotherapeutics. Knock-down of ZBTB16 entailed a small, but significant, increase in cell death induction by GC. Affymetrix Exon array-based whole genome expression profiling revealed that PLZF/ZBTB16 induction did not significantly alter the expression profile, however, it interfered with the regulation of numerous GC response genes, including BCL2L11/Bim, which has previously been shown to be responsible for cell death induction in CCRF-CEM cells. Thus, the protective effect of PLZF/ZBTB16 can be attributed to interference with transcriptional regulation by GC. |
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Authors:
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Muhammad Wasim; Michela Carlet; Muhammad Mansha; Richard Greil; Christian Ploner; Alexander Trockenbacher; Johannes Rainer; Reinhard Kofler |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-06 |
Journal Detail:
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Title: The Journal of steroid biochemistry and molecular biology Volume: 120 ISSN: 1879-1220 ISO Abbreviation: J. Steroid Biochem. Mol. Biol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-23 Completed Date: 2010-07-05 Revised Date: 2011-04-06 |
Medline Journal Info:
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Nlm Unique ID: 9015483 Medline TA: J Steroid Biochem Mol Biol Country: England |
Other Details:
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Languages: eng Pagination: 218-27 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Division Molecular Pathophysiology, Biocenter, Medical University of Innsbruck, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects* Cell Line, Tumor Child Gene Expression Regulation, Leukemic / drug effects* Glucocorticoids / pharmacology* Humans Kruppel-Like Transcription Factors / genetics*, metabolism* Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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F 2109//Austrian Science Fund FWF; P 18747-B13//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Glucocorticoids; 0/Kruppel-Like Transcription Factors; 147855-37-6/ZBTB16 protein, human |
| Comments/Corrections | |
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