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Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells

Elevated cAMP levels in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells attenuate the doxorubicin-induced p53 accumulation and protect cells against apoptosis. cAMP responsive element binding protein (CREB) is a cAMP-stimulated transcription factor that regulates genes whose deregulate...

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Autores principales: Manafi Shabestari, Rima, Safa, Majid, Banan, Mehdi, Kazemi, Ahmad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Babol University of Medical Sciences 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353983/
https://www.ncbi.nlm.nih.gov/pubmed/28357198
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author Manafi Shabestari, Rima
Safa, Majid
Banan, Mehdi
Kazemi, Ahmad
author_facet Manafi Shabestari, Rima
Safa, Majid
Banan, Mehdi
Kazemi, Ahmad
author_sort Manafi Shabestari, Rima
collection PubMed
description Elevated cAMP levels in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells attenuate the doxorubicin-induced p53 accumulation and protect cells against apoptosis. cAMP responsive element binding protein (CREB) is a cAMP-stimulated transcription factor that regulates genes whose deregulated expression cooperate in oncogenesis. In the present study, we investigated the role of CREB on inhibitory effect of cAMP on apoptosis and p53 accumulation in BCP-ALL NALM-6 cells. To determine whether targeting CREB can modulate the effect of cAMP on doxorubicin-induced apoptosis, we knocked down CREB in NALM-6 cells using lentiviral CREB shRNA. Knocked down cells were treated with doxorubicin in the presence or absence of cAMP-elevating agents. p53 protein level and apoptosis were assessed by western blot analysis and flow cytometry, respectively. p53 protein expression was reduced in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone even in CREB-knocked down cells. Apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis in CREB-knocked down and control cells. Although, CREB plays a particularly important role in cAMP signaling pathway our data suggest that CREB does not mediate the inhibitory effect of cAMP on doxorubicin-induced apoptosis and p53 accumulation in BCP-ALL NALM-6 cells.
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spelling pubmed-53539832017-03-29 Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells Manafi Shabestari, Rima Safa, Majid Banan, Mehdi Kazemi, Ahmad Int J Mol Cell Med Original Article Elevated cAMP levels in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells attenuate the doxorubicin-induced p53 accumulation and protect cells against apoptosis. cAMP responsive element binding protein (CREB) is a cAMP-stimulated transcription factor that regulates genes whose deregulated expression cooperate in oncogenesis. In the present study, we investigated the role of CREB on inhibitory effect of cAMP on apoptosis and p53 accumulation in BCP-ALL NALM-6 cells. To determine whether targeting CREB can modulate the effect of cAMP on doxorubicin-induced apoptosis, we knocked down CREB in NALM-6 cells using lentiviral CREB shRNA. Knocked down cells were treated with doxorubicin in the presence or absence of cAMP-elevating agents. p53 protein level and apoptosis were assessed by western blot analysis and flow cytometry, respectively. p53 protein expression was reduced in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone even in CREB-knocked down cells. Apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis in CREB-knocked down and control cells. Although, CREB plays a particularly important role in cAMP signaling pathway our data suggest that CREB does not mediate the inhibitory effect of cAMP on doxorubicin-induced apoptosis and p53 accumulation in BCP-ALL NALM-6 cells. Babol University of Medical Sciences 2016 2017-01-18 /pmc/articles/PMC5353983/ /pubmed/28357198 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Manafi Shabestari, Rima
Safa, Majid
Banan, Mehdi
Kazemi, Ahmad
Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells
title Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells
title_full Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells
title_fullStr Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells
title_full_unstemmed Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells
title_short Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells
title_sort cyclic amp-induced p53 destabilization is independent of creb in pre-b acute lymphoblastic leukemia cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353983/
https://www.ncbi.nlm.nih.gov/pubmed/28357198
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