Analysis of differential gene expression profiles of gastric cancer cells established from primary tumor and malignant ascites

胃癌原发灶与恶性腹水细胞基因表达谱的差异分析摘要进展期胃癌常伴有腹膜转移，死亡率高。胃癌转移的机制尚未完全阐明，因为转移涉及多个步骤，需要许多不同基因表达改变的组合。因此，对任何单个基因的独立分析都不足以了解胃癌腹膜播散的所有方面。在这项研究中，我们进行了一个全球性的差异基因表达的胃癌细胞系建立从一个主要的肿瘤（SNU-1）和其他细胞系建立从转移到腹腔（SNU-5，SNU-16，SNU-620，KATO-III和GT3 TKB）的分析。高密度cDNA微阵列技术的应用使得分析表达序列标签（ESTs）成为可能。分析R ...更多信息 观察到以下改变的表达，如：（a）上调CD 44（细胞粘附），角蛋白7、8和14（上皮标记），醛脱氢酶（药物代谢），CD 9和IP 3受体类型3（信号转导）;（B）IL 2受体γ、IL 4-Stat（免疫应答）、p27（细胞周期）和整合素β4（粘附）在恶性腹水胃癌细胞中的表达。然后，我们用北方印迹分析了8个胃癌细胞系，并观察到这些选定的基因在易于腹膜播散的细胞中的优先上调和下调。RT-PCR证实，基因芯片筛选出的几个基因在临床恶性腹水标本中也有过表达。因此认为这些基因可能与胃癌的腹膜播散有关。这一胃癌细胞腹膜播散的整体基因表达分析的结果，有望为人类胃癌腹膜播散的研究提供新的见解

Differential gene expression profiles of gastric cancer cells established from primary tumor and malignant ascites Abstract Advanced gastric cancer is often accompanied by metastasis to the peritoneum, resulting in high mortality rate. Mechanisms involved in gastric cancer metastasis have not been fully clarified because metastasis involves multiple steps and requires a combination of altered expressions of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer peritoneal dissemination. In this study, we performed a global analysis of the differential gene expression of a gastric cancer cell line established from a primary main tumor (SNU-1) and of other cell lines established from the metastasis to the peritoneal cavity (SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB). The application of a high-density Cdna microarray method made it possible to analyze the expression sequence tags (ESTs). The analysis r … More evealed the following altered expression such as: (a) up-regulation of CD44 (cell adhesion), keratin 7, 8 and 14 (epitherial marker), aldehyde dehydrogenase (drug metabolism), CD9 and IP3 receptor type3 (signal transduction); (b) down-regulation of IL2 receptor y, IL4-Stat (immune response), p27 (cell cycle) and integrin β4 (adhesion) in gastric cancer cells from malignant ascites. We then analyzed eight gastric cancer cell lines with Northern blot and observed preferential up-regulation and down-regulation of these selected genes in cells prone to peritoneal dissemination. RT-PCR confirmed that several genes selected by DNA microarray were also overexpressed in clinical samples of malignant ascites. It is therefore considered that these genes may be related to the peritoneal dissemination of gastric cancers. The results of this global gene expression analysis of gastric cancer cells with peritoneal dissemination, promise to provide a new insight into the study of human gastric cancer peritoneal dissemination Less