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Gene silencing of TSPYL5 mediated by aberrant promoter methylation in gastric cancers

Cited 30 time in Web of Science Cited 30 time in Scopus
Authors
Jung, Yeonjoo; Park, Jinah; Bang, Yung-Jue; Kim, Tae-You
Issue Date
2007-12-07
Publisher
Nature Publishing Group
Citation
Lab Invest. 2008;88(2):153-160
Keywords
Adenocarcinoma/*genetics/metabolism/pathologyCell Line, TumorCpG IslandsDNA MethylationEpigenesis, GeneticExonsGene ExpressionGenes, Tumor SuppressorHumansNuclear Proteins/*genetics/metabolismPromoter Regions, GeneticStomach Neoplasms/*genetics/metabolism/pathology
Abstract
DNA methylation is crucial for normal development, but gene expression altered by DNA hypermethylation is often associated with human diseases, especially cancers. The gene TSPYL5, encoding testis-specific Y-like protein, was previously identified in microarray screens for genes induced by the inhibition of DNA methylation and histone deacetylation in glioma cell lines. The TSPYL5 showed a high frequency of DNA methylation-mediated silencing in both glioma cell lines and primary glial tumors. We now report that TSPYL5 is also inactivated by DNA methylation and could be a putative epigenetic target gene in gastric cancers. We found that the expression of TSPYL5 mRNA was frequently downregulated and inversely correlated with DNA methylation in seven out of nine gastric cancer cell lines. TSPYL5 mRNA expression was also restored after treating with a DNA methyltransferase inhibitor. In primary gastric tumors, methylation-specific PCR results in 23 of the 36 (63.9%) cases revealed that the hypermethylation at CpG islands of the TSPYL5 was detectable at a high frequency. Furthermore, TSPYL5 suppressed the growth of gastric cancer cells as demonstrated by a colony formation assay. Thus, strong associations between TSPYL5 expression and hypermethylation were observed, and aberrant methylation at a CpG island of TSPYL5 may play an important role in development of gastric cancers.
ISSN
1530-0307 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18059362

http://www.nature.com/labinvest/journal/v88/n2/pdf/3700706a.pdf

http://hdl.handle.net/10371/68206
DOI
https://doi.org/10.1038/labinvest.3700706
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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