STUDIES ON GASTRIN RECEPTOR GENE EXPRESSION IN HUMAN GASTROINTESTINAL CARCINOMAS

1)利用人胃泌素受体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。胃癌细胞系和胃癌组织均无胃泌素受体基因表达。然而，两种小细胞胃癌细胞系中的一种（ECC10）明确表达胃泌素受体基因。2)胃泌素对结肠癌细胞株LoVo的生长有促进作用，而对ecc3细胞的生长无影响。3)在所有的肿瘤组织和癌细胞系中，我们未检测到胃泌素受体基因的突变。4)将人胃泌素受体cDNA转染到NIH3T3细胞后，胃泌素显著促进了NIH3T3细胞的生长。此外，胃泌素不仅能促进MAP激酶和黏附激酶酪氨酸磷酸化，还能激活MAP激酶。5)胃泌素刺激c-fos和c-myc基因在转染细胞中的表达。6)胃泌素诱导转染细胞形成肌动蛋白应激纤维，增强其流动性。7)综上所述，胃泌素受体基因在几种人类胃肠道肿瘤中均有表达，提示胃泌素参与了这些胃肠道肿瘤的生长。此外，还发现胃泌素通过激活酪氨酸激酶级联来促进细胞生长。此外，胃泌素可能通过影响肿瘤细胞骨架来影响肿瘤细胞的转移能力。

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.