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STUDIES ON GASTRIN RECEPTOR GENE EXPRESSION IN HUMAN GASTROINTESTINAL CARCINOMAS

人类胃肠癌胃泌素受体基因表达的研究

基本信息

批准号：
05454246
负责人：
CHIBA Tsutomu
金额：
$ 3.84万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454246/
关键词：
gastrin CCK-B gastrin receptor gastrin receptor gene Small cell gastric carcinoma MAP kinase focal adhesion kinase CCK-A受容体肺小細胞癌胃カルチノイド腫瘍 ECLカルチノイド大腸癌

项目摘要

1) By using human gastrin receptor cDNA,gastrin receptor mRNA expression was observed in nearly half of human small cell lung carcinoma tissues and cell lines, respectively. On the other hand, 10% of colon cancer cell lines and 20% of colon cancer tissues expressed gastrin receptor gene. In contrast, none of gastric cancer cell lines or gastric cancer tissues had gastrin receptor gene expression. However, one of the two small cell gastric carcinoma cell lines (ECC10) clearly expressed gastrin receptor gene.2) Gastrin enhanced the growth of a colon cancer cell line, LoVo, whereas it did not affect the growth of ECC10.3) In all the cancer tissues and cancer cell lines examined, we could not detect any mutated gastrin receptor gene.4) When transfecting human gastrin receptor cDNA into NIH3T3 cells, gastrin significantly enhanced the growth of these cells. Furthermore, gastrin not only promoted tyrosine phosphorylation of MAP kinase and focal adhesion kinase but also activated MAP kinase.5) Gastrin stimulated c-fos as well as c-myc gene expression in the transfected cells.6) Gastrin induced formation of actin stress fibers in the transfected cells, and enhanced their mobility.7) In summary, gastrin receptor genes are expressed in several human gastrointestinal carcinomas, suggesting that gastrin is involved in the growth of those gastrointestinal tumors. Furthermore, it was found that gastrin promotes the cell growth through activation of tyrosine kinase cascade. In addition, it was suggested that gastrin may influence the metastatic ability of the tumor cells by affecting cytoskeleton of the cells.

1)应用人胃泌素受体cDNA，分别在近一半的人小细胞肺癌组织和细胞系中观察到胃泌素受体mRNA的表达。另一方面，10%的结肠癌细胞系和20%的结肠癌组织表达胃泌素受体基因。相反，胃癌细胞系或胃癌组织中没有胃泌素受体基因表达。2）胃泌素对结肠癌细胞株LoVo的生长有促进作用，而对ECC 10的生长没有影响; 3）在所有的癌组织和癌细胞株中，我们都没有检测到任何突变的胃泌素受体基因; 4）将人胃泌素受体cDNA转染NIH 3 T3细胞，胃泌素显著促进这些细胞的生长。此外，胃泌素不仅促进MAP激酶和黏着斑激酶的酪氨酸磷酸化，而且激活MAP激酶。5）胃泌素刺激转染细胞中c-fos和c-myc基因的表达。6）胃泌素诱导转染细胞中肌动蛋白应力纤维的形成，并增强其运动性。7）总之，胃泌素受体基因在几种人胃肠道癌中表达，表明胃泌素参与了这些胃肠道肿瘤的生长。此外，发现胃泌素通过激活酪氨酸激酶级联反应促进细胞生长。此外，胃泌素可能通过影响细胞骨架而影响肿瘤细胞的转移能力。