Department of Pathology, The Wexner Medical Center at the Ohio State University, 410 W, 10th Avenue, Columbus, OH, 43210, USA.
Diagn Pathol. 2013 Dec 10;8:201. doi: 10.1186/1746-1596-8-201.
Protein arginine methyltransferase-5 (PRMT5) is a chromatin-modifying enzyme capable of methylating histone and non-histone proteins, and is involved in a wide range of cellular processes that range from transcriptional regulation to organelle biosynthesis. As such, its overexpression has been linked to tumor suppressor gene silencing, enhanced tumor cell growth and survival.
Quantitative real-time polymerase chain reaction, Western immunoblot and immunohistochemistry were used to characterize PRMT5 expression in lung cancer cell lines and human tumors. Clinicopathological findings of tissue microarray based samples from 229 patients with non-small cell lung carcinomas (NSCLC) and 133 cases with pulmonary neuroendocrine tumors (NET) were analyzed with regard to nuclear and cytoplasmic PRMT5 expression.
There was statistically significant difference in PRMT5 messenger RNA expression between tumors and nonneoplastic lung tissues. Immunoblot experiments showed abundant expression of PRMT5 and its symmetric methylation mark H4R3 in lung carcinoma but not in non-neoplastic human pulmonary alveolar and bronchial epithelial cell lines. More than two thirds of lung tumors expressed PRMT5. High levels of cytoplasmic PRMT5 were detected in 20.5% of NSCLC and in 16.5% of NET; high levels of nuclear PRMT5 were detected in 38.0% of NSCLC and 24.0% of NET. Cytoplasmic PRMT5 was associated with high grade in both NSCLC and pulmonary NET while nuclear PRMT5 was more frequent in carcinoid tumors (p < 0.05).
The observed findings support the role of PRMT5 in lung tumorigenesis and reflect its functional dichotomy in cellular compartments.
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1611895162102528.
蛋白质精氨酸甲基转移酶-5（PRMT5）是一种能够甲基化组蛋白和非组蛋白的染色质修饰酶，参与从转录调控到细胞器生物合成等广泛的细胞过程。因此，其过表达与肿瘤抑制基因沉默、增强肿瘤细胞生长和存活有关。
使用定量实时聚合酶链反应、Western 免疫印迹和免疫组织化学方法来描述肺癌细胞系和人类肿瘤中的 PRMT5 表达。对 229 例非小细胞肺癌（NSCLC）和 133 例肺神经内分泌肿瘤（NET）组织微阵列样本的临床病理发现，分析核和细胞质 PRMT5 表达。
肿瘤和非肿瘤性肺组织之间的 PRMT5 信使 RNA 表达存在统计学显著差异。免疫印迹实验显示 PRMT5 及其对称甲基化标记 H4R3 在肺癌中大量表达，但在非肿瘤性人肺泡和支气管上皮细胞系中没有表达。超过三分之二的肺癌表达 PRMT5。在 20.5%的 NSCLC 和 16.5%的 NET 中检测到高水平的细胞质 PRMT5；在 38.0%的 NSCLC 和 24.0%的 NET 中检测到高水平的核 PRMT5。细胞质 PRMT5 在 NSCLC 和肺 NET 中与高分级相关，而核 PRMT5 在类癌中更为常见（p<0.05）。
观察到的发现支持 PRMT5 在肺肿瘤发生中的作用，并反映了其在细胞区室中的功能二分法。
