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Cellular localization of protein arginine methyltransferase-5 correlates with grade of lung tumors

Konstantin Shilo1*, Xin Wu2, Smita Sharma3, Meng Welliver3, Wenrui Duan2, Miguel Villalona-Calero2, Junya Fukuoka4, Said Sif5, Robert Baiocchi2, Charles L Hitchcock1, Weiqiang Zhao1 and Gregory A Otterson2

Author Affiliations

1 Department of Pathology, The Wexner Medical Center at the Ohio State University, 410 W. 10th Avenue, Columbus, OH, 43210, USA

2 Department of Medicine, The Wexner Medical Center at the Ohio State University, Columbus, OH, USA

3 Department of Radiology, The Wexner Medical Center at the Ohio State University, Columbus, OH, USA

4 Department of Pathology, Nagasaki University School of Medicine, Nagasaki, Japan

5 Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, USA

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Diagnostic Pathology 2013, 8:201  doi:10.1186/1746-1596-8-201

Published: 10 December 2013

Abstract

Background

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.

Material and methods

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.

Results

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 (pā€‰<ā€‰0.05).

Conclusion

The observed findings support the role of PRMT5 in lung tumorigenesis and reflect its functional dichotomy in cellular compartments.

Virtual slide

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1611895162102528 webcite

Keywords:
Protein arginine methyltransferase-5; Lung carcinoma; Neuroendocrine tumors