Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas.
Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas.
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星形胶质瘤和正常脑组织中的12个组蛋白脱乙酰基酶（HDAC）基因的差异表达：II和IV类在胶质母细胞瘤中不表达。
DOI：
10.1186/1471-2407-8-243
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发表时间：
2008-08-19
期刊：
影响因子：
3.8
通讯作者：
Tone LG
中科院分区：
文献类型：
--
作者：
Lucio-Eterovic AK;Cortez MA;Valera ET;Motta FJ;Queiroz RG;Machado HR;Carlotti CG Jr;Neder L;Scrideli CA;Tone LG
胶质母细胞瘤是最致命的原发性恶性脑肿瘤。虽然在治疗这种侵袭性肿瘤方面取得了相当大的进展，但患者的临床结局仍然很差。组蛋白去乙酰化酶（HDAC）被认为是癌症治疗的有希望的靶点。在过去的几年中，HDAC抑制剂（HDACis）已被用作胶质母细胞瘤治疗中的放射增敏剂。然而，还没有研究表明胶质瘤中HDAC的整体表达状况及其与HDACis使用的可能相关性。本研究的目的是评估和比较低级别和高级别星形细胞瘤和正常脑组织中HDACs I、II和IV类的mRNA和蛋白水平，并将结果与星形细胞瘤的恶性程度相关联。对43个显微切割的患者肿瘤样本进行了评价。组织病理学诊断为20例低级别胶质瘤（13例I级和7例II级）和23例高级别胶质瘤（5例III级和18例胶质母细胞瘤）。还分析了11份正常脑组织样本（共分析了54份样本）。通过定量实时聚合酶链反应研究I、II和IV类HDAC的mRNA表达，并将其标准化为管家基因β-葡萄糖醛酸苷酶。通过蛋白质印迹法评价蛋白质水平。我们发现，与低级别星形细胞瘤和正常脑组织相比，胶质母细胞瘤中II类和IV类HDAC的mRNA水平下调（8个基因中有7个，p < 0.05）。高级别星形细胞瘤中II类HDAC 9的蛋白水平也低于低级别星形细胞瘤和正常脑组织。此外，我们发现组蛋白H3（而不是组蛋白H4）在胶质母细胞瘤中比正常脑组织更乙酰化。我们的研究建立了HDAC基因表达与胶质瘤分级之间的负相关性，表明II和IV类HDAC可能在胶质瘤恶性度中起重要作用。组蛋白乙酰化水平的评估显示，组蛋白H3在胶质母细胞瘤中比正常脑组织中乙酰化程度更高，证实了胶质母细胞瘤中HDAC mRNA的下调。
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. 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. 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. 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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DOI：
10.1111/j.1349-7006.2001.tb02153.x
发表时间：
2001-12
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Choi JH;Kwon HJ;Yoon BI;Kim JH;Han SU;Joo HJ;Kim DY
通讯作者：
Kim DY
影响因子：
6.4
作者：
Camphausen, K;Cerna, D;Tofilon, PJ
通讯作者：
Tofilon, PJ
影响因子：
4.8
作者：
Gao, L;Cueto, MA;Atadja, P
通讯作者：
Atadja, P
影响因子：
2.9
作者：
Kölle, D;Brosch, G;Loidl, P
通讯作者：
Loidl, P
影响因子：
3.4
作者：
Jiang, Rongcai;Mircean, Cristian;Zhang, Wei
通讯作者：
Zhang, Wei