The human gastrin/cholecystokinin receptors: type B and type C expression in colonic tumors and cell lines.

The CCK-type B receptors are recognized by gastrin, which is known to be possibly involved in the development of gastro-intestinal cancers; alternate splicing of exon 4 of the human CCK-B receptor gene gives 2 different mRNA isoforms, the exact significance of which still remains to be elucidated. The recently described CCK-type C receptors recognize gastrin but do not discriminate between mature and immature forms of the hormone. A series of healthy and tumoral colon samples, the associated hepatic metastases and four colonic cell lines were examined for gene expression of the 2 isoforms of the CCK-B receptor and the CCK-C receptor using reverse transcription-polymerase chain reaction. Gastrin mRNA expression was also investigated. The short isoform of the CCK-B was detected in 80% of the normal colon tissues, 76.5% of the colon tumors, 100% of the metastasis samples and 75% of the colonic cell lines; whereas the long isoform, which is presumably more strongly activated by gastrin, was expressed in 50% of the normal colon samples, 23% of the colon tumors, 43% of the hepatic metastases and 1 cell line (Sk-Co15). However, although CCK-C transcript was detected in 100% of the tumors tested and gastrin mRNA in 86.5%, only 16.5% also expressed the long isoform of the CCK-B receptor. The gastrin/CCK-B receptor might therefore be involved in an hypothetic autocrine proliferative loop only in some colonic tumors, and the receptor mainly involved in this loop may well be the CCK-C receptor, since its mRNA is expressed as often as gastrin mRNA in tumors and cell lines.