EXPRESSION OF THE GASTRIN GENE IN THE NORMAL HUMAN COLON AND COLORECTAL ADENOCARCINOMA

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 ga strointestinal tract. Because of its possible role in colon cell proli feration and differentiation, evidence for its presence in normal colo rectal mucosa and adenocarcinoma was sought. Utilizing tumors and matc hed normal mucosa from 26 patients, mature gastrin and progastrin were studied by immunohistochemistry. In normal colonic mucosal crypts, oc casional cells stained concordantly for gastrin, progastrin, and chrom ogranin A, suggesting that they are of neuroendocrine origin. Adenomat ous 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 polym erase chain reaction and RNase protection in tumors and by polymerase chain reaction in normal mucosa. Its identity was confirmed by sequenc ing the polymerase chain reaction product. A larger transcript contain ing Intron II was present in both cancers and normal mucosa but was ba rely discernible in the gastric antrum. Aberrant expression of gastrin may contribute to deregulated proliferation of many colorectal carcin omas.