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PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
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 wi...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Pergamon
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892747/ https://www.ncbi.nlm.nih.gov/pubmed/20435142 http://dx.doi.org/10.1016/j.jsbmb.2010.04.019 |
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author | Wasim, Muhammad Carlet, Michela Mansha, Muhammad Greil, Richard Ploner, Christian Trockenbacher, Alexander Rainer, Johannes Kofler, Reinhard |
author_facet | Wasim, Muhammad Carlet, Michela Mansha, Muhammad Greil, Richard Ploner, Christian Trockenbacher, Alexander Rainer, Johannes Kofler, Reinhard |
author_sort | Wasim, Muhammad |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2892747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Pergamon |
record_format | MEDLINE/PubMed |
spelling | pubmed-28927472010-07-15 PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis Wasim, Muhammad Carlet, Michela Mansha, Muhammad Greil, Richard Ploner, Christian Trockenbacher, Alexander Rainer, Johannes Kofler, Reinhard J Steroid Biochem Mol Biol Article 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. Pergamon 2010-06 /pmc/articles/PMC2892747/ /pubmed/20435142 http://dx.doi.org/10.1016/j.jsbmb.2010.04.019 Text en © 2010 Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license |
spellingShingle | Article Wasim, Muhammad Carlet, Michela Mansha, Muhammad Greil, Richard Ploner, Christian Trockenbacher, Alexander Rainer, Johannes Kofler, Reinhard PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis |
title | PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis |
title_full | PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis |
title_fullStr | PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis |
title_full_unstemmed | PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis |
title_short | PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis |
title_sort | plzf/zbtb16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892747/ https://www.ncbi.nlm.nih.gov/pubmed/20435142 http://dx.doi.org/10.1016/j.jsbmb.2010.04.019 |
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