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Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas

BACKGROUND: Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In...

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Autores principales: Lucio-Eterovic, Agda KB, Cortez, Maria AA, Valera, Elvis T, Motta, Fabio JN, Queiroz, Rosane GP, Machado, Helio R, Carlotti, Carlos G, Neder, Luciano, Scrideli, Carlos A, Tone, Luiz G
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536671/
https://www.ncbi.nlm.nih.gov/pubmed/18713462
http://dx.doi.org/10.1186/1471-2407-8-243
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author Lucio-Eterovic, Agda KB
Cortez, Maria AA
Valera, Elvis T
Motta, Fabio JN
Queiroz, Rosane GP
Machado, Helio R
Carlotti, Carlos G
Neder, Luciano
Scrideli, Carlos A
Tone, Luiz G
author_facet Lucio-Eterovic, Agda KB
Cortez, Maria AA
Valera, Elvis T
Motta, Fabio JN
Queiroz, Rosane GP
Machado, Helio R
Carlotti, Carlos G
Neder, Luciano
Scrideli, Carlos A
Tone, Luiz G
author_sort Lucio-Eterovic, Agda KB
collection PubMed
description BACKGROUND: Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global HDAC expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas. METHODS: Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV HDACs was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene β-glucuronidase. Protein levels were evaluated by western blotting. RESULTS: We found that mRNA levels of class II and IV HDACs were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, p < 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue. CONCLUSION: Our study establishes a negative correlation between HDAC gene expression and the glioma grade suggesting that class II and IV HDACs might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of HDAC mRNA in glioblastomas.
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spelling pubmed-25366712008-09-16 Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas Lucio-Eterovic, Agda KB Cortez, Maria AA Valera, Elvis T Motta, Fabio JN Queiroz, Rosane GP Machado, Helio R Carlotti, Carlos G Neder, Luciano Scrideli, Carlos A Tone, Luiz G BMC Cancer Research Article BACKGROUND: Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global HDAC expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas. METHODS: Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV HDACs was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene β-glucuronidase. Protein levels were evaluated by western blotting. RESULTS: We found that mRNA levels of class II and IV HDACs were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, p < 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue. CONCLUSION: Our study establishes a negative correlation between HDAC gene expression and the glioma grade suggesting that class II and IV HDACs might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of HDAC mRNA in glioblastomas. BioMed Central 2008-08-19 /pmc/articles/PMC2536671/ /pubmed/18713462 http://dx.doi.org/10.1186/1471-2407-8-243 Text en Copyright © 2008 Lucio-Eterovic et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lucio-Eterovic, Agda KB
Cortez, Maria AA
Valera, Elvis T
Motta, Fabio JN
Queiroz, Rosane GP
Machado, Helio R
Carlotti, Carlos G
Neder, Luciano
Scrideli, Carlos A
Tone, Luiz G
Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas
title Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas
title_full Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas
title_fullStr Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas
title_full_unstemmed Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas
title_short Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas
title_sort differential expression of 12 histone deacetylase (hdac) genes in astrocytomas and normal brain tissue: class ii and iv are hypoexpressed in glioblastomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536671/
https://www.ncbi.nlm.nih.gov/pubmed/18713462
http://dx.doi.org/10.1186/1471-2407-8-243
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