STUDIES ON GASTRIN RECEPTOR GENE EXPRESSION IN HUMAN GASTROINTESTINAL CARCINOMAS

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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.