Analysis of 11p15 locus in gastric cancer

胃癌11p15位点分析

基本信息

批准号：
14570135
负责人：
UOZAKI Hiroshi
金额：
$ 2.18万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570135/
关键词：
Gastric cancer 11p15 MUC Epstein-Barr virus Fetal stomach 11q15

项目摘要

We investigated the chromosome 11p15 locus of gastric cancer (GC). The 11p15 locus was focused through Genechip TM assay of SCID mouse transplantable Epstein-Barr virus (EBV)-associated GC strain. In this study, MUC genes were focused among the genes located on 11p15. Expression of MUC2,5AC, and 6 determinates mucin phenotype of GC ; gastric type, intestinal type, mixed type, and null type.We examined 74 cases of GC immunohistochemically and found that EBVaGC is likely to be null phenotype and gastric phenotype. It is a contrast to EBV negative GC, almost of which shows either gastric or intestinal phenotype. EBVaGC shows decrease of CK7 expression immunohistochemically. From both results of mucin and cytokeratin expression, EBVaGC is thought to be close to stem cells of gastric mucosa.Next we examined DNA methylation status of MUC2 and MUC5AC genes by digestion with methylation sensitive restricted enzyme, HpaII, followed by PCR Among 22 GC cases, 8 cases were MUC2 positive and 11 cases MUC5AC positive immunohistochemically. Whereas all cases showed methylated status of MUC2 and MUC5AC gene. There were no correlation between immunohistochemical positivity and DNA methylation status of MUC2 and 5AC.We examined 6 GC cell lines. We have got EBV infected sublines of all 6 cell lines using recombinant EBV. Immunocytochemically TMK1 decrease MUC2 after EBV infection. It was not associated with change of DNA methylation status. MUC5AC expression was not influenced by EBV infection, but TMK1, MKN-1, and NU-GC-3 increased DNA methylation at MUC5AC locus after EBV infection. The result of the cell line study is consistent with the fact that EBVaGC shows high rate of DNA methylation of tumor related genes.

我们研究了胃癌11p15染色体（GC）。 11P15基因座通过对SCID小鼠移植爱泼斯坦 - 巴尔病毒（EBV）相关的GC菌株的Genechip TM分析进行聚焦。在这项研究中，MUC基因集中在11p15上的基因中。 MUC2,5AC的表达和6个确定GC的粘蛋白表型；胃类型，肠道类型，混合类型和无效类型。我们在74例GC免疫组织化学上检查了EBVAGC可能是无效的表型和胃表型。这与EBV负GC形成鲜明对比，EBV负GC几乎显示了胃或肠表型。 EBVAGC在免疫组织化学上显示了CK7表达的降低。从粘蛋白和细胞角蛋白表达的两个结果中，EBVAGC被认为接近胃粘膜的干细胞。NEXT我们检查了MUC2和MUC5AC基因的DNA甲基化状态，并通过甲基化敏感性限制的酶，HPAII，HPAII，PCR在22例GC病例中，然后是8例MUC2阳性，MUC2阳性和11例MUC2 muc2 muc2阳性。而所有病例均显示MUC2和MUC5AC基因的甲基化状态。 MUC2和5AC的免疫组织化学阳性与DNA甲基化状态之间没有相关性。我们检查了6个GC细胞系。使用重组EBV，我们已经获得了所有6个细胞系的EBV感染subline。免疫细胞化学上TMK1在EBV感染后降低MUC2。它与DNA甲基化状态的变化无关。 MUC5AC表达不受EBV感染的影响，但是TMK1，MKN-1和NU-GC-3在EBV感染后MUC5AC基因座上增加了DNA甲基化。细胞系研究的结果与EBVAGC显示出高肿瘤相关基因的DNA甲基化速率的事实一致。