Net1 and Myeov: computationally identified mediators of gastric cancer.

Net1 and Myeov: computationally identified mediators of gastric cancer.
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DOI:
10.1038/sj.bjc.6603054
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发表时间:
2006-04-24
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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胃腺癌(GA)是世界范围内的一个重要死亡原因。GA的分子机制仍然很差的特点。我们的目的是验证GA中计算鉴定的基因NET 1和MYEOV的功能活性。利用数字差异显示技术对GA EST文库中表达改变的基因进行鉴定。在一组细胞系和肿瘤组织中,通过qPCR定量一组基因的mRNA水平。研究了促炎和抗炎刺激对基因表达的影响。在使用siRNA抑制表达后,在体外GA模型中测量细胞增殖和侵袭。在所有的,23个基因没有以前报道与GA被确定。选择两个基因Net1和Myeov用于进一步分析,并且使用定量PCR在GA组织中检测到与配对的正常组织相比增加的表达。siRNA介导的Net1和Myeov下调导致胃癌细胞体外增殖和侵袭能力下降。这些功能研究强调了NET1和Myeov在胃癌发展和进展中的假定作用。这些基因可以提供GA干预的重要靶点,其在促进癌细胞的关键表型标志侵袭和增殖中的作用证明了这一点。
Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells.
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