Unit of Pathology, Cannizzaro Hospital, Catania, Italy.
Eur J Histochem. 2012 Feb 27;56(1):e9. doi: 10.4081/ejh.2012.e9.
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 8,000 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.
成人中最常见的原发性脑肿瘤之一是多形性胶质母细胞瘤（GBM）（世界卫生组织四级星形细胞瘤）。它是最常见的恶性和侵袭性神经胶质瘤，也是最致命的肿瘤之一。位于 1q42 的多聚（ADP-核糖）聚合酶 1（PARP-1）基因在维持基因组完整性方面起着重要作用。PARP-1 蛋白对于凋亡诱导因子（AIF）从线粒体到细胞核的易位是必需的。PARP-1 在凋亡起始时被半胱天冬酶-3 蛋白水解切割。超过 8000 个样本的 PARP-1 基因表达的微阵列分析表明，与相应的正常组织相比，PARP-1 在几种类型的癌症中表达更高。总体而言，PARP-1 基因表达的差异在乳腺癌、卵巢癌、子宫内膜癌、肺癌和皮肤癌以及非霍奇金淋巴瘤中最为明显。我们通过免疫组织化学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 样本中均发现了阳性核 PARP-1 染色，但在对照（n=4）和 GBM 患者（n=27）的正常神经元中未发现阳性染色。在任何样本中均未观察到细胞质染色。总之，PARP-1 基因在 GBM 中表达。这一发现可以被设想为试图在这种肿瘤以及许多其他恶性肿瘤中触发细胞凋亡。该蛋白仅存在于细胞核中，进一步支持了该基因在维持基因组完整性和凋亡中的作用。最后，PARP-1 染色可作为 GBM 细胞标志物。
