Research Papers:

Glutathione peroxidase 7 suppresses cancer cell growth and is hypermethylated in gastric cancer

Zheng Chen, Tianling Hu, Shoumin Zhu, Kenichi Mukaisho, Wael El-Rifai and Dun-Fa Peng _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:54345-54356. https://doi.org/10.18632/oncotarget.17527

Metrics: PDF 2348 views  |   HTML 2822 views  |   ?  


Zheng Chen1, Tianling Hu1, Shoumin Zhu1, Kenichi Mukaisho5, Wael El-Rifai1,2,3,4 and Dun-Fa Peng1

1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

2Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

3Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA

4Department of Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA

5Department of Pathology, Division of Molecular Diagnostic Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan

Correspondence to:

Dun-Fa Peng email: [email protected]

Keywords: GPX7, stomach, cancer, DNA methylation, tumor suppressor

Received: March 17, 2017     Accepted: April 14, 2017     Published: April 29, 2017


Gastric cancer (GC) is one of the most common cancers in the world, and remains the third leading cause of cancer-related deaths worldwide. Glutathione peroxidase 7 (GPX7) is a member of GPX family which is downregulated in some cancer types. In this study, we investigated the expression, regulation, and molecular function of GPX7 in gastric cancer using 2D and 3D in vitro models and de-identified human tissue samples. Quantitative real-time RT-PCR, immunofluorescence, Western blot, 3D organotypic cultures, and pyrosequencing assays were used. We detected downregulation of GPX7 in all 7 gastric cancer cell lines that we tested and in approximately half (22/45) of human gastric cancer samples, as compared to histologically normal gastric tissues. Quantitative bisulfite pyrosequencing methylation analysis demonstrated DNA hypermethylation (> 10% methylation level) of GPX7 promoter in all 7 gastric cancer cell lines and in 56% (25/45) of gastric cancer samples, as compared to only 13% (6/45) in normal samples (p < 0.0001). Treatment of AGS and SNU1 cells with 5-Aza-2′-deoxycytidine led to a significant demethylation of GPX7 promoter and restored the expression of GPX7. In vitro assays showed that reconstitution of GPX7 significantly suppressed gastric cancer cell growth in both 2D and 3D organotypic cell culture models. This growth suppression was associated with inhibition of cell proliferation and induction of cell death. We detected significant upregulation of p27 and cleaved PARP and downregulation of Cyclin D1 upon reconstitution of GPX7. Taken together, we conclude that epigenetic silencing of GPX7 could play an important role in gastric tumorigenesis and progression.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 17527