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STUDY ON THE SIGNIFICANCE OF GASTRIN RECEPTOR GENE EXPRESSION IN HUMAN GASTROINTESTINAL CARCINOMAS

胃泌素受体基因表达在人类胃肠癌中的意义研究

基本信息

批准号：
07457136
负责人：
CHIBA Tsutomu
金额：
$ 4.16万
依托单位：
KYOTO UNIVERSITY (1996)Kobe University (1995)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457136/
关键词：
Gastric Carcinoid Gastric Cancer Gastric endocrine cell carcinoma Gastrin receptor GATA protein Parietal cell 大腸癌ガストリン RAS イノシトールリン脂質代謝回転ガストリン拮抗剤

项目摘要

1.In human gastrointestinal tumors, gastrin receptor genes are expressed in gastric ECL carcinoid tumors, endocrine cell carcinoma of the stomach and colon cancers, whereas no expression of gastrin receptor gene is observed in any gastric carcinomas.2.In a human gastric endocrine carcinoma cell line ECC10, gastrin enhanced inositolphospholipid turnover with resulting increase of [Ca^<2+>] i.Moreover, gastrin elicited not only activation of Ras and MAP kinase but also expression of c-fos gene.3.By foot-printing method, several binding sites for nuclear extracts from ECC10 or LoVo cells were detected on the upstream of gastrin receptor gene. In addition to APl site, another binding site for nuclear protein was identified as GATA binding domain.4.Since both HK-ATPase gene and histamine H^2 receptor gene possess GATA binding domains, we examined whether the nuclear extracts from parietal cells, which express both HK-ATPase and H_2 receptors, can bind to the GATA binding domain of the gastrin receptor gene, and it was found that the nuclear extracts from canine parietal cells could bind to the GATA binding domain of the receptor gene.5.When the expression of GATA binding protein was investigated both LoVo cells and ECC10 cells, which express gastrin receptors, were found to have significant expressior..of the GATA binding proteins. In contrast, its expression was not observed in other carcinoma cells which did not express gastrin receptor genes.6.Thus, GATA binding protein plays an important role in the expression of gastrin receptor gene not only in parietal cells but also in various cancer cells.

1.在人胃肠道肿瘤中，胃泌素受体基因在胃ECL类癌、胃内分泌细胞癌和结肠癌中表达，而在任何胃癌中均未观察到胃泌素受体基因的表达。2.在人胃内分泌癌细胞系ECC 10中，胃泌素增强肌醇磷脂的转换，导致[Ca^<2+>] i增加。胃泌素不仅能激活Ras和MAP激酶，还能诱导c-fos基因的表达。3.足迹法检测到在胃泌素受体基因上游有多个与ECC 10和LoVo细胞核提取物结合的位点。由于HK-ATP酶基因和组胺H_2受体基因都具有加塔结合结构域，我们检测了同时表达HK-ATP酶和H_2受体的壁细胞核提取物是否能与胃泌素受体基因的加塔结合结构域结合，结果表明，犬壁细胞核提取物可与胃泌素受体基因的加塔结合域结合。5.加塔结合蛋白的表达在表达胃泌素受体的LoVo细胞和ECC 10细胞中均有显著表达。加塔结合蛋白。因此，加塔结合蛋白不仅在壁细胞中，而且在各种癌细胞中，对胃泌素受体基因的表达起着重要的作用。