https://scholars.lib.ntu.edu.tw/handle/123456789/187493
標題: | DNA Methylation and Histone Modification Regulate Silencing of Epithelial Cell Adhesion Molecule for Tumor Invasion and Progression | 作者: | Tai, K-Y Shiah, S-G Shieh, Y-S Kao, Y-R Chi, C-Y Huang, E Lee, H-S Chang, L-C Yang, P-C Wu, C-W 楊泮池 |
關鍵字: | Ep-CAM;invasion;promoter methylation | 公開日期: | 2007 | 卷: | v.26 | 期: | n.27 | 起(迄)頁: | 3989-3997 | 來源出版物: | ONCOGENE | 摘要: | Epithelial cell adhesion molecule ( Ep-CAM) is believed to have a critical role in carcinogenesis and cell proliferation. However, the association of Ep-CAM with cancer invasion and progression is less clear. We found that EpCAM was highly expressed on low-invasive cells compared with highly invasive cells. Forced expression of Ep-CAM decreased cancer invasiveness, and silencing Ep-CAM expression elevated cancer invasiveness . EpCAM expression was associated with promoter methylation. Treatment with a demethylating agent, and/or the histone deacetylase inhibitor reactivated Ep-CAM expression in Ep-CAM-negative cells and inhibited cancer invasiveness. Using a promoter- reporter construct, we demonstrated methylation of the promoter fragment drive Ep-CAM-silenced transcription. Additionally, silenced Ep-CAM gene in cancer cells was enriched for hyper -methylated histone 3 lysine 9. When unmethylated and active, this promoter was associated with acetylated histone 3 lysine 9. Furthermore, we observed an increased association of Ep-CAM promoter with repression components as tumor invasiveness increased. In cancer tissues, Ep-CAM expression significantly correlated with tumor progression and associated with promoter methylation. Our data support the idea that modulation of Ep -CAM plays a pivotal role in tumor invasion and progression. Moreover, aberrant DNA methylation of Ep-CAM is implicated in enhancing invasive/ metastatic proclivity of tumors. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/88335 |
顯示於: | 醫學系 |
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