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食道・胃接合部癌発生におけるムチン分子ファミリー遺伝子及び糖鎖の役割

粘蛋白分子家族基因和糖链在食管胃结合部癌发生中的作用

基本信息

批准号：
09877110
负责人：
遠藤高夫
金额：
$ 1.22万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Exploratory Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Barrett上皮(short segment Barrettを含む),Barrett腺癌,下部食道腺癌について各種ムチンコア蛋白(MUC1,MUC2,MUC3),Oグリコシド型ムチン糖鎖(91.9H 4D3,M1),p53の発現を検討し,Barrett上皮→intestinal type metaplasia→adenocarcinomaに至る過程を検討した.なお91.9HはSO_3-Galβ1-3(Fucα1-4)GlcNAcを認識し大腸型ムチンで,4D3はNANA-GalNAc類似糖鎖を認識し小腸型ムチン,M1(Baraら)は胃型ムチンの代表と考えられる.1. ムチンコア蛋白の発現MUC1はBarrett上皮に79%,下部食道腺癌の42.9%にまたMUC2はそれぞれ33.3%,42.9%に発現していたが,MUC3の発現は認められなかった.MUC1は組織特異性はなく上皮に一様に見られたが,MUC2はBarrett上皮のintestinal type epitheliumにのみ見られ.juctional typeやfundic typeには陰性であった.しかしながら癌化に伴う有意の発現上昇は観察されなかった.2. ムチン糖鎖ならびにM1の発現Barrett上皮で大腸型ムチンは50%,小腸型ムチンは30%,胃型ムチンは60%に検出された.組織分布を見ると大腸型と小腸型はintestinal type上皮に見られ,胃型はfundicおよびjunctional type上皮に見られた.腺癌では大腸型ムチンは92%,小腸型ムチンは42%,胃型ムチンは8%に見られた.Barrett上皮の長さによってこれらの発現を検討するといわゆるshot segment Barrett上皮は胃型のムチン優位で,classical Barrett上皮では大腸型のムチンが強く発現していた.また腺癌を伴うBarrett上皮では大腸型が,腺癌を伴わないBarrett上皮では胃型が強く発現していた.3. ムチン糖鎖とコア蛋白の関連4D3(NANA-GalNAc類似糖鎖)のapomucinはMUC2と推定されたが,91.9Hのapomucinは今回の実験では不明であった.以上よりBarrett上皮(short segment→classical Barrett)→intestinal type metaplasia→adenocarcinomaの過程でムチンは徐々に硫酸化糖鎖を持つ大腸型が優位になり,胃型の粘液形質は減少した.これは胃における不完全型腸上皮化生からの腸型胃癌の発生に類似している.

Barrett's epithelium (short segment Barrett),Barrett's adenocarcinoma, lower esophageal adenocarcinoma, various kinds of protein (MUC1, MUC2, MUC3), O-type protein (91.9H4D3,M1),p53 gene expression were investigated. Barrett's epithelium →intestinal type metaplasia→adenocarcinoma were investigated. <$91.9H SO_3-Galβ1-3(Fucα1-4)GlcNAc MUC1 was found in 79% of Barrett epithelium, MUC2 in 42.9% of lower esophageal adenocarcinoma, MUC3 in 42.9% of lower esophageal adenocarcinoma. MUC1 was found in tissue-specific epithelium, MUC2 was found in intestinal type epithelium, and MUC3 was found in fundic type. The cancer is accompanied by an intentional rise in the number of cases detected. 2. Barrett epithelium was detected in 50% of large intestine type, 30% of small intestine type and 60% of stomach type. Tissue distribution: large intestine type, small intestine type, intestinal type, stomach type, fundic type, junctional type. Adenocarcinoma was found in 92%, 42%, and 8%, respectively.Barrett epithelium was found in 92%, small intestine in 42%, and stomach in 8%.Barrett epithelium was found in 92%, stomach in 42%, and classical Barrett epithelium in 82%. Adenocarcinoma accompanied by Barrett epithelium, large intestine type, adenocarcinoma accompanied by Barrett epithelium, stomach type, strong development. 3. The apomucin MUC2 of NANA-GalNAc-like glycan chain was putative, and the apomucin of 91.9H was putative. Barrett epithelium (short segment→classical Barrett)→intestinal type metaplasia→ adenocarcinomaThe process of large intestine type metaplasia remains optimal, while gastric type mucus decreases. The development of incomplete intestinal metaplasia and intestinal gastric cancer is similar.