X-linked ectodermal dysplasia receptor is downregulated in breast cancer via promoter methylation.
X-linked ectodermal dysplasia receptor is downregulated in breast cancer via promoter methylation.
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DOI：
10.1158/1078-0432.ccr-09-2463
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发表时间：
2010-02-15
期刊：
影响因子：
--
通讯作者：
Chaudhary PM
中科院分区：
文献类型：
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作者：
Punj V;Matta H;Chaudhary PM
The X-linked ectodermal dysplasia receptor (XEDAR) is a novel receptor of the Tumor Necrosis Factor Receptor Family that binds to ectodysplasin-A2 (EDA-A2) and induces cell death. The purpose of this study was to determine the tumor-suppressive potential of XEDAR in the development of breast cancer. We analyzed the expression of XEDAR in breast cancer cell lines and tumor samples using quantitative real-time RT-PCR analysis and immunoblotting. We analyzed the human XEDAR gene promoter for the presence of any CpG island and examined its methylation status using methylation-specific real-time PCR. We examined the effect of 5-aza-2′-deoxycytidine (5-Aza-dC) on the expression of XEDAR and sensitivity to EDA-A2-induced apoptosis in breast cancer cell lines. Expression of XEDAR, but not EDA-A2, was downregulated in most tumorigenic breast cancer cell lines and tumor samples. Loss of XEDAR expression correlated with the hypermethylation of its promoter. Ectopic expression of XEDAR in MDA-MB-231 cells resulted in significant induction of apoptosis and reduction in colony formation. Treatment with 5-Aza-dC restored XEDAR expression in breast cancer cell lines with methylated XEDAR promoter and sensitized them to EDA-A2-induced cell death. Our results suggest that XEDAR expression is down-regulated in most breast cancers via promoter methylation, which may contribute to accelerated tumor development by blocking EDA-A2-induced cell death. XEDAR may represent a novel breast tumor suppressor gene and restoration of its expression by treatment with DNA demethylating agents may represent an attractive approach for the treatment of breast cancer.
