| Summary: | <p>Abstract</p> <p>Background</p> <p>Downregulation of the putative tumor suppressor gene <it>SLC22A18 </it>has been reported in a number of human cancers. The aim of this study was to investigate the relationship between <it>SLC22A18 </it>downregulation, promoter methylation and the development and progression of human glioma.</p> <p>Method</p> <p><it>SLC22A18 </it>expression and promoter methylation was examined in human gliomas and the adjacent normal tissues. U251 glioma cells stably overexpressing <it>SLC22A18 </it>were generated to investigate the effect of <it>SLC22A18 </it>on cell growth and adherence <it>in vitro </it>using the methyl thiazole tetrazolium assay. Apoptosis was quantified using flow cytometry and the growth of <it>SLC22A18 </it>overexpressing U251 cells was measured in an <it>in viv</it>o xenograft model.</p> <p>Results</p> <p><it>SLC22A18 </it>protein expression is significantly decreased in human gliomas compared to the adjacent normal brain tissues. <it>SLC22A18 </it>protein expression is significantly lower in gliomas which recurred within six months after surgery than gliomas which did not recur within six months. <it>SLC22A18 </it>promoter methylation was detected in 50% of the gliomas, but not in the adjacent normal tissues of any patient. SLC22A18 expression was significantly decreased in gliomas with <it>SLC22A18 </it>promoter methylation, compared to gliomas without methylation. The <it>SLC22A18 </it>promoter is methylated in U251 cells and treatment with the demethylating agent 5-aza-2-deoxycytidine increased <it>SLC22A18 </it>expression and reduced cell proliferation. Stable overexpression of <it>SLC22A18 </it>inhibited growth and adherence, induced apoptosis <it>in vitro </it>and reduced <it>in vivo </it>tumor growth of U251 cells.</p> <p>Conclusion</p> <p><it>SLC22A18 </it>downregulation via promoter methylation is associated with the development and progression of glioma, suggesting that <it>SLC22A18 </it>is an important tumor suppressor in glioma.</p>
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