Promoter methylation and downregulation of SLC22A18 are associated with the development and progression of human glioma
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Chu et al. Journal of Translational Medicine 2011, 9:156 http://www.translational-medicine.com/content/9/1/156
RESEARCH
Open Access
Promoter methylation and downregulation of SLC22A18 are associated with the development and progression of human glioma Sheng-Hua Chu1*, Dong-Fu Feng1, Yan-Bin Ma1, Hong Zhang1, Zhi-An Zhu1, Zhi-Qiang Li2 and Pu-Cha Jiang2
Abstract Background: Downregulation of the putative tumor suppressor gene SLC22A18 has been reported in a number of human cancers. The aim of this study was to investigate the relationship between SLC22A18 downregulation, promoter methylation and the development and progression of human glioma. Method: SLC22A18 expression and promoter methylation was examined in human gliomas and the adjacent normal tissues. U251 glioma cells stably overexpressing SLC22A18 were generated to investigate the effect of SLC22A18 on cell growth and adherence in vitro using the methyl thiazole tetrazolium assay. Apoptosis was quantified using flow cytometry and the growth of SLC22A18 overexpressing U251 cells was measured in an in vivo xenograft model. Results: SLC22A18 protein expression is significantly decreased in human gliomas compared to the adjacent normal brain tissues. SLC22A18 protein expression is significantly lower in gliomas which recurred within six months after surgery than gliomas which did not recur within six months. SLC22A18 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 SLC22A18 promoter methylation, compared to gliomas without methylation. The SLC22A18 promoter is methylated in U251 cells and treatment with the demethylating agent 5-aza-2-deoxycytidine increased SLC22A18 expression and reduced cell proliferation. Stable overexpression of SLC22A18 inhibited growth and adherence, induced apoptosis in vitro and reduced in vivo tumor growth of U251 cells. Conclusion: SLC22A18 downregulation via promoter methylation is associated with the development and progression of glioma, suggesting that SLC22A18 is an important tumor suppressor in glioma.
Background Gliomas are a major class of human intrinsic brain tumors, which includes well differentiated low grade astrocytomas, anaplastic astrocytomas and glioblastoma multiforme, the most malignant brain tumor of adulthood. Although resection remains the most effective treatment for glioma, the high rate of postoperative recurrence inevitably leads to a poor clinical outcome. In an effort to develop novel potential effective treatments, recent studies have focused on understanding the molecular pathogenesis of glioma formation and progression. Gliomas are frequently characterized by invasion and * Correspondence: [email protected] 1 Department of Neurosurgery, NO.3 People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China Full list of author information is available at the end of the article
growth [1] and are hypothesized to form in a multistage p
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