Molecular Pathology Laboratory, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Molecular Pathology Laboratory, Institute of Medical Science, the University of Tokyo, Tokyo, Japan; Department of Integrative Pathology, Jichi Medical University, Tochigi, Japan.
Hum Pathol. 2014 Jul;45(7):1397-405. doi: 10.1016/j.humpath.2014.02.013. Epub 2014 Feb 28.
Although protein arginine methyltransferase 5 (PRMT5) has been implicated in various cancers, its expression pattern in lung adenocarcinoma cell lines and tissues has not been elucidated enough. In this study, microarray analysis of 40 non-small-cell lung carcinoma cell lines showed that PRMT5 was a candidate histone methyltransferase gene that correlated with epithelial-mesenchymal transition. Immunocytochemical analysis of these cell lines indicated that the expression of PRMT5 was localized to the cytoplasm of E-cadherin-low and vimentin-high cell lines, whereas it was predominant in the nucleus and faint in the cytoplasm of E-cadherin-high and vimentin-low cell lines. Immunohistochemical analysis of lung adenocarcinoma cases (n = 130) revealed that the expression of PRMT5 was high in the cytoplasm of 47 cases (36%) and the nuclei of 34 cases (26%). The marked cytoplasmic expression of PRMT5 was frequently observed in high-grade subtypes (1 of 17 low grade, 21 of 81 intermediate grade, and 25 of 32 high grade; P < .0001) such as solid adenocarcinoma with the low expression of thyroid transcription factor 1 (the master regulator of lung) and low expression of cytokeratin 7 and E-cadherin (2 markers for bronchial epithelial differentiation), whereas the high nuclear expression of PRMT5 was frequently noted in adenocarcinoma in situ, a low-grade subtype (6 of 17 low grade, 25 of 81 intermediate grade, and 3 of 32 high grade; P = .0444). The cytoplasmic expression of PRMT5 correlated with a poor prognosis (P = .0089). We herein highlighted the importance of PRMT5 expression, especially its cytoplasmic expression, in the process of epithelial-mesenchymal transition and loss of the bronchial epithelial phenotype of lung adenocarcinoma.
尽管蛋白质精氨酸甲基转移酶 5（PRMT5）已被牵涉到多种癌症中，但它在肺腺癌细胞系和组织中的表达模式尚未得到充分阐明。在这项研究中，对 40 种非小细胞肺癌细胞系进行了微阵列分析，结果表明 PRMT5 是一种候选组蛋白甲基转移酶基因，与上皮-间充质转化相关。对这些细胞系的免疫细胞化学分析表明，PRMT5 的表达定位于 E-钙黏蛋白低和波形蛋白高的细胞系的细胞质中，而在 E-钙黏蛋白高和波形蛋白低的细胞系中则主要位于核内，细胞质中较弱。对 130 例肺腺癌病例的免疫组织化学分析显示，47 例（36％）的细胞质和 34 例（26％）的细胞核中 PRMT5 表达较高。在高级别亚型（17 例低级别中的 1 例，81 例中级别的 21 例和 32 例高级别的 25 例；P<.0001）中，如甲状腺转录因子 1（肺的主调控因子）低表达、细胞角蛋白 7 和 E-钙黏蛋白（支气管上皮分化的 2 个标志物）低表达的实性腺癌中，PRMT5 的细胞质表达常呈明显阳性，而在原位腺癌（低级别亚型）中，PRMT5 的核表达较高（6 例低级别，25 例中级别和 32 例高级别；P=.0444）。PRMT5 的细胞质表达与预后不良相关（P=.0089）。我们在此强调了 PRMT5 表达，特别是其细胞质表达，在肺腺癌上皮-间充质转化和支气管上皮表型丧失过程中的重要性。
