Expression but incomplete maturation of progastrin in colorectal carcinomas.
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/10(6) cells). Two cell lines secreted progastrin into the media (LoVo, 25 +/- 3 pmol/L; HCT116; 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.
Van Solinge
W W
WW
University Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Nielsen
F C
FC
Friis-Hansen
L
L
Falkmer
U G
UG
Rehfeld
J F
JF
D000199:Actins / Q000235:genetics; D000230:Adenocarcinoma / Q000378:metabolism*; D015152:Blotting, Northern; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005091:Exons; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012004:Rectal Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000199:Actins; D005755:Gastrins; D009838:Oligodeoxyribonucleotides; D011498:Protein Precursors; D015347:RNA Probes; D012333:RNA, Messenger; C013706:big gastrin