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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Research

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

Authors: Konstantin Shilo, Xin Wu, Smita Sharma, Meng Welliver, Wenrui Duan, Miguel Villalona-Calero, Junya Fukuoka, Said Sif, Robert Baiocchi, Charles L Hitchcock, Weiqiang Zhao, Gregory A Otterson

Published in: Diagnostic Pathology | Issue 1/2013

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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 (p < 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.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​1611895162102528​
Appendix
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Metadata
Title
Cellular localization of protein arginine methyltransferase-5 correlates with grade of lung tumors
Authors
Konstantin Shilo
Xin Wu
Smita Sharma
Meng Welliver
Wenrui Duan
Miguel Villalona-Calero
Junya Fukuoka
Said Sif
Robert Baiocchi
Charles L Hitchcock
Weiqiang Zhao
Gregory A Otterson
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-201

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