Yeh Kun-Tu, Tang Kai-Ping, Chen Yao-Li, Su Wei-Wen, Wang Yu-Fen, Chang Jan-Gowth
Department of Molecular Medicine, China Medical University, Taichung, Taiwan.
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
Cancer Genomics Proteomics. 2006 May-Aug;3(3-4):231-238. Epub 2006 Jan 1.
CDS1 is an enzyme required for the regeneration of the signaling molecule phosphatidylinositol-4,5-bisphosphate (PIP2) from phosphatidic acid. These phosphoinositides and their cleavage products are a class of second messengers, which are involved in cell growth and oncogenesis. The role of CDS1 in the development of hepatocellular carcinoma (HCC) was explored.
The expression of CDS1 in 52 HCC and paired non-cancer tissues was examined by real-time quantitative reverse transcription-polymerase chain reaction analysis.
The results showed that the expression levels of CDS1 significantly decreased in HCC. However, no mutation was found within the coding region. Interestingly, in the promoter area of the CDS1 gene, most of the CpG sites were methylated in 73% of the cancer tissues; in contrast, only a partial methylation of CpG was found in 50% of the non-cancer tissues.
Our results suggested that the down-regulated CDS1 expression in HCC was due to the inactivation of the CDS1 gene by methylation and that the differential expression correlated to the ratio of CpG sites being methylated.
CDS1是一种从磷脂酸再生信号分子磷脂酰肌醇-4,5-二磷酸(PIP2)所必需的酶。这些磷酸肌醇及其裂解产物是一类第二信使,参与细胞生长和肿瘤发生。本研究探讨了CDS1在肝细胞癌(HCC)发生发展中的作用。
采用实时定量逆转录-聚合酶链反应分析检测52例HCC组织及配对的癌旁组织中CDS1的表达。
结果显示,HCC组织中CDS1的表达水平显著降低。然而,在编码区内未发现突变。有趣的是,在CDS1基因的启动子区域,73%的癌组织中大部分CpG位点发生甲基化;相比之下,50%的癌旁组织中仅发现部分CpG位点甲基化。
我们的结果表明,HCC中CDS1表达下调是由于甲基化导致CDS1基因失活,且差异表达与CpG位点甲基化比例相关。