原發性肺癌CD44基因之表現與DNA之甲基化的關係(2/2)

Abstract

CD44 是位於細胞表面的分子, 是細胞外基質hyaluronan 的受體. 細胞可藉著其表面 的CD44 分子黏附於細胞外基質, 淋巴球可藉著其表面的CD44 分子黏附於淋巴結 內之high endothelial venules, 癌細胞亦可藉著其表面的CD44 分子黏附於基質, 造 成轉移. 本計劃主持人在前一年度之計劃曾發現, 肺腺癌惡化時, CD44v6 之表現會 減弱, 其機轉尚不明. 本計劃即研究肺癌CD44 基因之轉錄調控區之甲基化情形, 目 的是觀察CD44 基因之表現受到抑制是否與其轉錄調控區中CpG sites 之甲基化有關. 方法是將15 個手術切除之肺腺癌組織的genomic DNA 抽出後, 經過bisulfite 處理, 再以PCR 增量CD44 基因之轉錄調控區, 然後作DNA 序列分析, 找出此調控區中6 個CpG sites 之甲基化情形. 結果發現肺腺癌CD44v6 之表現與其轉錄調控區中 CpG sites 之甲基化之間並無顯著之關係.

Methylation of the CD44 promoter at one or more CpG dinucleotides has been proposed as being important in the control of CD44 expression. In our previous study we found CD44 was down-regulated in patients with more advanced stages of pulmonary adenocarcinoma. Therefore in this study we examined the methylation status of the 6 CpG sites in the promoter region upstream the CD44 gene translation initiation site by genomic sequencing using differential base modification by sodium bisulfite. In 15 tumor samples of the surgically resected pulmonary adenocarcinoma, we found there was no consistent relationship between methylation status of any of these 6 CpG sites and the expression of the CD44v6 protein as studied by immunohistochemical staining.