Downregulation of ARFGEF1 and CAMK2B by promoter hypermethylation in breast cancer cells
Downregulation of ARFGEF1 and CAMK2B by promoter hypermethylation in breast cancer cells
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DOI：
10.5483/bmbrep.2011.44.8.523
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发表时间：
2011-08-31
期刊：
影响因子：
3.8
通讯作者：
Kim, Sun Jung
中科院分区：
文献类型：
--
作者：
Kim, Ju Hee;Kim, Tae Woo;Kim, Sun Jung
为了鉴定受启动子甲基化调控的新基因，进行了包括计算机挖掘和分子测定的组合方法。从欧洲生物信息学研究所（FBI）注册的表达微阵列dab中，首先筛选在乳腺癌细胞中显示下调的基因，然后使用Unigene数据库通过e-Northem分析选择。一系列计算机模拟方法将CAMK 2B和ARFGEF 1确定为候选基因，这两个基因在乳腺癌细胞系中被高甲基化，在正常乳腺细胞系中被低甲基化。此外，癌细胞系显示这些基因的表达下调。此外，用去甲基化剂5-氮杂-2 '-脱氧胞苷处理癌细胞系，恢复了CAMK 2B和ARFGEF 1的表达，这意味着高甲基化沉默了癌细胞中的基因活性。总之，CAMK 2B和ARFGEF 1的启动子甲基化是在乳腺癌细胞系中鉴定的新的表观遗传标记，并且可以用于临床癌症组织的应用。[BMB报告2011; 44（8）：523-528]
To identify novel genes that are regulated by promoter methylation, a combinational approach involving in silico mining followed by molecular assay was performed. From the expression microarray dab registered in the European bioinformatics institute (FBI), genes showing downregulation in breast cancer cells were initially screened and then selected by e-Northem analysis using the Unigene database. A series of these in silico methods identified CAMK2B and ARFGEF1 as candidates, and the two genes were revealed to be hypermethylated in breast cancer cell lines and hypomethylated in normal breast cell lines. Additionally, cancer cell lines showed downregulated expression of these genes. Furthermore, treatment of the cancer cell lines with a demethylation agent, 5-Aza-2'-deoxycytidine, recovered expression of CAMK2B and ARFGEF1, implying that hypermethyaltion silenced gene activity in cancer cells. Taken together, promoter methylations of CAMK2B and ARFGEF1 are novel epigenetic markers identified in breast cancer cell lines and can be utilized for the application to clinical cancer tissues. [BMB reports 2011; 44(8): 523-528]