Gastrin in human bronchogenic carcinomas: constant expression but variable processing of progastrin

Using a library of radioimmunoassays against essential sequences of human progastrin and procholecystokinin, we have examined the occurrence of gastrin, cholecystokinin, and their precursors in bronchogenic adenocarcinomas, large-cell, small-cell, and squamous-cell carcinomas (n = 17). Progastrin and some of its bioactive (i.e., alpha-carboxyamidated) products were present in all tumors, irrespective of histological classification. The concentration of progastrin varied from 0.2 to 21.9 pmol/g tissue; glycine-extended intermediates constituted less than 0.1 to 0.5 pmol/g; and bioactive, carboxyamidated gastrin ranged from less than 0.1 to 6.1 pmol/g. Chromatography showed that the bioactive gastrins were exclusively gastrin-17 peptides, half of which were tyrosine O-sulfated. Neither procholecystokinin nor its processing products were found in the tumor extracts. Six samples of nonneoplastic human lung tissue contained traces of progastrin (range, less than 0.1-0.8 pmol/g), but neither bioactive gastrins nor any cholecystokinin. The results show that the gastrin gene is expressed in all classes of bronchogenic carcinomas. Due to incomplete posttranslational processing measurement of progastrin may be necessary to detect such expression.