PARP-1 protein expression in glioblastoma multiforme.

PARP-1 protein expression in glioblastoma multiforme.
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DOI:
10.4081/ejh.2012.e9
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发表时间:
2012-02-27
期刊:
European journal of histochemistry : EJH
影响因子:
--
通讯作者:
Salemi M
Salemi M
中科院分区:
其他
文献类型:
--
作者:
Galia A;Calogero AE;Condorelli R;Fraggetta F;La Corte A;Ridolfo F;Bosco P;Castiglione R;Salemi M

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成人中最常见的原发性脑肿瘤类型之一是多形性胶质母细胞瘤(GBM)(世界卫生组织IV级星形细胞瘤)。它是胶质瘤最常见的恶性和侵袭性形式,并且是最致命的形式之一。聚腺苷二磷酸核糖聚合酶1(Poly(ADP-ribose)polymerase 1,PARP-1)基因位于染色体1 q42,在维持基因组完整性中起重要作用。PARP-1蛋白是凋亡诱导因子(AIF)从线粒体转运到细胞核所必需的。PARP-1在凋亡开始时被caspase-3蛋白水解裂解。在超过8000个样本中的PARP-1基因表达的微阵列分析显示,与相当的正常组织相比,PARP-1在几种类型的癌症中的表达更高。总体而言,在乳腺癌、卵巢癌、子宫内膜癌、肺癌和皮肤癌以及非霍奇金淋巴瘤中观察到PARP-1基因表达的最大差异。我们通过免疫组织化学方法评估了正常脑组织和原发性GBM中PARP-1蛋白的表达。在所有GBM样本中均发现阳性核PARP-1染色,但在对照组(n=4)和GBM患者(n=27)的正常神经元中未发现。在所有样品中均未观察到细胞质染色。结论:PARP-1基因在GBM中有表达。这一发现可能被设想为试图在这种肿瘤中以及在许多其他恶性肿瘤中引发细胞凋亡。该蛋白仅存在于细胞核进一步支持该基因在基因组完整性维持和细胞凋亡中发挥的功能。最后,PARP-1染色可用作GBM细胞标志物。
One of the most common type of primary brain tumors in adults is the glioblastoma multiforme (GBM) (World Health Organization grade IV astrocytoma). It is the most common malignant and aggressive form of glioma and it is among the most lethal ones. Poly (ADP-ribose) polymerase 1 (PARP-1) gene, located to 1q42, plays an important role for the efficient maintenance of genome integrity. PARP-1 protein is required for the apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. PARP-1 is proteolytically cleaved at the onset of apoptosis by caspase-3. Microarray analysis of PARP-1 gene expression in more than 8000 samples revealed that PARP-1 is more highly expressed in several types of cancer compared with the equivalent normal tissues. Overall, the most differences in PARP-1 gene expression have been observed in breast, ovarian, endometrial, lung, and skin cancers, and non-Hodgkin's lymphoma. We evaluated the expression of PARP-1 protein in normal brain tissues and primary GBM by immunohistochemistry. Positive nuclear PARP-1 staining was found in all samples with GBM, but not in normal neurons from controls (n=4) and GBM patients (n=27). No cytoplasmic staining was observed in any sample. In conclusion, PARP-1 gene is expressed in GBM. This finding may be envisioned as an attempt to trigger apoptosis in this tumor, as well as in many other malignancies. The presence of the protein exclusively at the nucleus further support the function played by this gene in genome integrity maintenance and apoptosis. Finally, PARP-1 staining may be used as GBM cell marker.
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