TY - JOUR

T1 - Expression but incomplete maturation of progastrin in colorectal carcinomas

AU - van Solinge, Wouter W

AU - Nielsen, Finn C.

AU - Friis-Hansen, Lennart

AU - Falkmer, Ursula G.

AU - Rehfeld, Jens F.

PY - 1993

Y1 - 1993

N2 - Background: To evaluate the hypothesis that gastrin is a local growth factor in colonic carcinomas, the expression of gastrin messenger RNA (mRNA) and peptides were examined in five human colon carcinoma cell lines, 12 solid colon carcinomas, and normal colonic tissue. Methods: Northern analysis, reverse-transcription PCR, and a library of sequence-specific radioimmunoassays were the principal methods. Results: Cell lines, tumors, and normal tissue all expressed a gastrin mRNA of 0.7 kilobases, and all cell lines contained incompletely processed progastrin (range, 17-54 fmol/106 cells). Two cell lines secreted progastrin into the media (LoVo, 25 ± 3 pmol/L; HCT 116; 12 ± 2 pmol/L). Normal colonic tissue and all the solid tumors also contained progastrin, the concentration being higher in tumors (range, 0.4-2 pmol/g) than in normal tissue (range, 0.1-0.2 pmol/g). Only one tumor contained carboxyamidated gastrins. Conclusions: Normal and neoplastic colonic mucosa both express the gastrin gene, but the posttranslational phase of expression is attenuated. The incomplete processing and low level of expression suggest that autocrine gastrin secretion has only minor significance for normal adult and most neoplastic colonic tissue.

AB - Background: To evaluate the hypothesis that gastrin is a local growth factor in colonic carcinomas, the expression of gastrin messenger RNA (mRNA) and peptides were examined in five human colon carcinoma cell lines, 12 solid colon carcinomas, and normal colonic tissue. Methods: Northern analysis, reverse-transcription PCR, and a library of sequence-specific radioimmunoassays were the principal methods. Results: Cell lines, tumors, and normal tissue all expressed a gastrin mRNA of 0.7 kilobases, and all cell lines contained incompletely processed progastrin (range, 17-54 fmol/106 cells). Two cell lines secreted progastrin into the media (LoVo, 25 ± 3 pmol/L; HCT 116; 12 ± 2 pmol/L). Normal colonic tissue and all the solid tumors also contained progastrin, the concentration being higher in tumors (range, 0.4-2 pmol/g) than in normal tissue (range, 0.1-0.2 pmol/g). Only one tumor contained carboxyamidated gastrins. Conclusions: Normal and neoplastic colonic mucosa both express the gastrin gene, but the posttranslational phase of expression is attenuated. The incomplete processing and low level of expression suggest that autocrine gastrin secretion has only minor significance for normal adult and most neoplastic colonic tissue.

U2 - 10.1016/0016-5085(93)90279-L

DO - 10.1016/0016-5085(93)90279-L

M3 - Journal article

C2 - 8462798

AN - SCOPUS:0027480995

VL - 104

SP - 1099

EP - 1107

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 4

ER -