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

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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.