This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, Y. P. Articles by Luo, J.-H. Search for Related Content PubMed PubMed Citation Articles by Yu, Y. P. Articles by Luo, J.-H.

Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis

Departments of ¹ Pathology, ² Biostatistics, and ³ Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Requests for reprints: Jian-Hua Luo, Department of Pathology, University of Pittsburgh, 3550 Terrace Street, Scaife Hall A-725, Pittsburgh, PA 15261. Phone: 412-648-8791; Fax: 412-648-5997; E-mail: luoj{at}msx.upmc.edu.

Glutathione peroxidase 3 is a selenium-dependent enzyme playing a critical role in detoxifying reactive oxidative species and maintaining the genetic integrity of mammalian cells. In this report, we found that the expression of glutathione peroxidase 3 (GPx3) was widely inactivated in prostate cancers. Complete inactivation of GPx3 correlates with a poor clinical outcome. Deletions (hemizygous and homozygous) of GPx3 gene are frequent in prostate cancer samples, occurring in 39% of the samples studied. The rate of methylation of the GPx3 exon 1 region in prostate cancer samples reaches 90%. Overexpression of GPx3 in prostate cancer cell lines induced the suppression of colony formation and anchorage-independent growth of PC3, LNCaP, and Du145 cells. PC3 cells overexpressing GPx3 reduced invasiveness in Matrigel transmigration analysis by an average of 2.7-fold. Xenografted PC3 cells expressing GPx3 showed reduction in tumor volume by 4.8-fold, elimination of metastasis (0/16 versus 7/16), and reduction of animal death (3/16 versus 16/16). The tumor suppressor activity of GPx3 seems to relate to its ability to suppress the expression of c-met. The present findings suggest that GPx3 is a novel tumor suppressor gene. [Cancer Res 2007;67(17):8043–50]

This article has been cited by other articles:

				L. Chaiswing, W. Zhong, J. J. Cullen, L. W. Oberley, and T. D. Oberley Extracellular Redox State Regulates Features Associated with Prostate Cancer Cell Invasion Cancer Res., July 15, 2008; 68(14): 5820 - 5826. [Abstract] [Full Text] [PDF]

				N. Wakamatsu, J. B. Collins, J. S. Parker, M. Tessema, N. P. Clayton, T.-V. T. Ton, H.-H. L. Hong, S. Belinsky, T. R. Devereux, R. C. Sills, et al. Gene Expression Studies Demonstrate that the K-ras/Erk MAP Kinase Signal Transduction Pathway and Other Novel Pathways Contribute to the Pathogenesis of Cumene-induced Lung Tumors Toxicol Pathol, July 1, 2008; 36(5): 743 - 752. [Abstract] [Full Text] [PDF]