Differential expression of 12 histone deacetylase (<it>HDAC</it>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas
<p>Abstract</p> <p>Background</p> <p>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 r...
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| Format: | Article |
| Language: | English |
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BMC
2008-08-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/8/243 |
| _version_ | 1811249634809479168 |
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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 | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>HDAC </it>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.</p> <p>Methods</p> <p>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 <it>HDACs </it>was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene <it>β-glucuronidase</it>. Protein levels were evaluated by western blotting.</p> <p>Results</p> <p>We found that mRNA levels of class II and IV <it>HDACs </it>were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, <it>p </it>< 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.</p> <p>Conclusion</p> <p>Our study establishes a negative correlation between <it>HDAC </it>gene expression and the glioma grade suggesting that class II and IV <it>HDACs </it>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 <it>HDAC </it>mRNA in glioblastomas.</p> |
| first_indexed | 2024-04-12T15:51:06Z |
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| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T15:51:06Z |
| publishDate | 2008-08-01 |
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| spelling | doaj.art-c799c9a20c154d77a202c8e266a4d4ea2022-12-22T03:26:31ZengBMCBMC Cancer1471-24072008-08-018124310.1186/1471-2407-8-243Differential expression of 12 histone deacetylase (<it>HDAC</it>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomasLucio-Eterovic Agda KBCortez Maria AAValera Elvis TMotta Fabio JNQueiroz Rosane GPMachado Helio RCarlotti Carlos GNeder LucianoScrideli Carlos ATone Luiz G<p>Abstract</p> <p>Background</p> <p>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 <it>HDAC </it>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.</p> <p>Methods</p> <p>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 <it>HDACs </it>was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene <it>β-glucuronidase</it>. Protein levels were evaluated by western blotting.</p> <p>Results</p> <p>We found that mRNA levels of class II and IV <it>HDACs </it>were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, <it>p </it>< 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.</p> <p>Conclusion</p> <p>Our study establishes a negative correlation between <it>HDAC </it>gene expression and the glioma grade suggesting that class II and IV <it>HDACs </it>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 <it>HDAC </it>mRNA in glioblastomas.</p>http://www.biomedcentral.com/1471-2407/8/243 |
| spellingShingle | 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 (<it>HDAC</it>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas BMC Cancer |
| title | Differential expression of 12 histone deacetylase (<it>HDAC</it>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas |
| title_full | Differential expression of 12 histone deacetylase (<it>HDAC</it>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas |
| title_fullStr | Differential expression of 12 histone deacetylase (<it>HDAC</it>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas |
| title_full_unstemmed | Differential expression of 12 histone deacetylase (<it>HDAC</it>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas |
| title_short | Differential expression of 12 histone deacetylase (<it>HDAC</it>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas |
| title_sort | differential expression of 12 histone deacetylase it hdac it genes in astrocytomas and normal brain tissue class ii and iv are hypoexpressed in glioblastomas |
| url | http://www.biomedcentral.com/1471-2407/8/243 |
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