Home » Key Clinical Research Articles Global Medical Discovery » Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition

Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition

Ibrahim R1, Matsubara D2, Osman W1, Morikawa T3, Goto A4, Morita S3, Ishikawa S3, Aburatani H5, Takai D6, Nakajima J7, Fukayama M3, Niki T8, Murakami Y1.

Hum Pathol. 2014;45(7):1397-405.

1Molecular Pathology Laboratory, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.and

2Molecular Pathology Laboratory, Institute of Medical Science, the University of Tokyo, Tokyo, Japan; Department of Integrative Pathology, Jichi Medical University, Tochigi, Japan. Electronic address: [email protected]

3Human Pathology Department, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.and

4Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan.and

5Division of Genome Science, Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo, Japan.and

6Department of Clinical Laboratory, the University of Tokyo, Tokyo, Japan.and

7Department of Thoracic Surgery, the University of Tokyo, Tokyo, Japan.and

8Department of Integrative Pathology, Jichi Medical University, Tochigi, Japan.

 

Abstract

 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 thatPRMT5 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.

Copyright © 2014 Elsevier Inc. All rights reserved.

Go To PubMed