Dp71 Expression in Human Glioblastoma
Dp71 Expression in Human Glioblastoma
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DOI：
10.3390/ijms20215429
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Nico, Beatrice
中科院分区：
文献类型：
--
作者：
Ruggieri, Simona;De Giorgis, Michelina;Nico, Beatrice
背景：Dp 71是神经系统中最丰富的肌营养不良蛋白（DMD）基因产物。Dp 71编码区的突变与杜氏肌营养不良症（DMD）患者的认知障碍有关，但抗肌萎缩蛋白Dp 71在肿瘤进展中的功能仍有待确定。本研究探讨了Dp 71在胶质母细胞瘤中的表达，胶质母细胞瘤是中枢神经系统（CNS）最常见和最具侵袭性的原发性肿瘤。研究方法：通过免疫荧光、免疫组织化学、RT-PCR和免疫印迹分析胶质母细胞瘤细胞系和从人多形性胶质母细胞瘤（GBM）活检标本分离的细胞中的Dp 71表达。结果如下：Dp 71亚型在正常人星形胶质细胞（NHA）细胞系中表达，在胶质母细胞瘤细胞系和从人多形性胶质母细胞瘤活检标本分离的细胞中表达减少。此外，Dp 71在正常细胞中定位于细胞核，而在成胶质细胞瘤成簇细胞中定位于细胞质。我们已经表明，通过双标记，Dp 71与核纤层蛋白B在正常星形胶质细胞中共定位，证实了Dp 71和核纤层蛋白B在维持核结构中的作用。最后，我们证明，从人类活检标本分离的细胞中Dp 71蛋白的减少与Ki-67肿瘤增殖指数呈负相关。结论：胶质母细胞瘤中Dp 71表达降低与肿瘤增殖和预后不良有关。
Background: Dp71 is the most abundant dystrophin (DMD) gene product in the nervous system. Mutation in the Dp71 coding region is associated with cognitive disturbances in Duchenne muscular dystrophy (DMD) patients, but the function of dystrophin Dp71 in tumor progression remains to be established. This study investigated Dp71 expression in glioblastoma, the most common and aggressive primary tumor of the central nervous system (CNS). Methods: Dp71 expression was analyzed by immunofluorescence, immunohistochemistry, RT-PCR, and immunoblotting in glioblastoma cell lines and cells isolated from human glioblastoma multiforme (GBM) bioptic specimens. Results: Dp71 isoform was expressed in normal human astrocytes (NHA) cell lines and decreased in glioblastoma cell lines and cells isolated from human glioblastoma multiforme bioptic specimens. Moreover, Dp71 was localized in the nucleus in normal cells, while it was localized into the cytoplasm of glioblastoma cells organized in clusters. We have shown, by double labeling, that Dp71 colocalizes with lamin B in normal astrocytes cells, confirming the roles of Dp71 and lamin B in maintaining nuclear architecture. Finally, we demonstrated that decreased Dp71 protein in cells isolated from human bioptic specimens was inversely correlated with the Ki-67 tumor proliferative index. Conclusion: A decreased Dp71 expression is associated with cancer proliferation and poor prognosis in glioblastoma.