EXPRESSION OF GASTRIN, GASTRIN CCK-B AND GASTRIN/CCK-C RECEPTORS IN HUMAN COLORECTAL CARCINOMAS/

To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the recepto r responsible, 102 human colorectal carcinomas and 10 hepatic metastas es were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gastrin/CCK-C receptor. Levels of RNA expression were assayed by RNase protection assay. In addition, ga strin/CCK receptors on crude membranes of tumour tissue were assayed b y radioligand binding. High-affinity,gastrin/CCK-B receptors were not detected in any of the carcinomas investigated, whereas in 36% low-aff inity binding was observed, consistent with the expression of the gast rin/CCK-C receptor. RNase protection assay detected the RNA for the ga strin/CCK-B receptor in 11% of the carcinomas investigated, whereas th e RNA for the gastrin/CCK-C receptor was demonstrated in 75% and the R NA for gastrin in 86% of the carcinomas investigated. These results co nfirm the recent demonstration of progastrin fragments in colorectal c arcinomas. One possible explanation for progastrin expression is that such progastrin fragments may participate in an autocrine proliferativ e loop. The receptor involved in this loop is more likely to be the lo w-affinity gastrin/CCK-C receptor rather than the gastrin/CCK-B recept or, which is rarely expressed in colorectal carcinomas.