Gastrin, produced in the G-cells of the gastric antrum and regulating acid secretion in the stomach, also acts as a trophic factor in the gastrointestinal tract. Because of its possible role in colon cell proliferation and differentiation, evidence for its presence in normal colorectal mucosa and adenocarcinoma was sought. Utilizing tumors and matched normal mucosa from 26 patients, mature gastrin and progastrin were studied by immunohistochemistry. In normal colonic mucosal crypts, occasional cells stained concordantly for gastrin, progastrin, and chromogranin A, suggesting that they are of neuroendocrine origin. Adenomatous polyps stained neither for gastrin nor chromogranin A. In 22 of 23 adenocarcinomas, more than 50% of tumor cells stained for gastrin and progastrin. The expected gastrin transcript was demonstrable by polymerase chain reaction and RNase protection in tumors and by polymerase chain reaction in normal mucosa. Its identity was confirmed by sequencing the polymerase chain reaction product. A larger transcript containing Intron II was present in both cancers and normal mucosa but was barely discernible in the gastric antrum. Aberrant expression of gastrin may contribute to deregulated proliferation of many colorectal carcinomas.
Supported in part by a Merit Review Grant from the Veterans Administration and by Amgen, Inc.