Characterization of gastrin-releasing peptide receptors aberrantly expressed by non-antral gastric adenocarcinomas.
Epithelial cells lining the GI tract except in the gastric antrum do not normally express gastrin-releasing peptide receptors (GRP-R). Because GRP-R activation causes the proliferation of many GI cancer cell lines, aberrant expression has been presumed to negatively influence patient survival. We therefore determined the incidence and quality of GRP-R aberrantly expressed by non-antral gastric adenocarcinomas, and evaluated the impact of receptor expression on patient survival. We studied RNA isolated from 20 consecutive non-antral gastric adenocarcinomas, and determined that 8 (40%) aberrantly expressed GRP-R. Of these, 6 (75%) were found to be mutated. Pharmacologically, the effect of these mutations ranged from rendering the GRP-R non-functional to constitutively active. Contrary to expectations, however, survival of patients whose tumor expressed functional GRP-R (18.5 +/- 9.8 months) was not statistically different from those that did not (8.3 +/- 1.8 months; p = 0.24). Thus our data indicate that mutated isoforms of GRP-R are commonly expressed by non-antral gastric adenocarcinomas. However, expression of functional GRP-R does not alter patient survival, suggesting that this receptor may not be clinically important to the growth of gastric cancers.
Carroll
R E
RE
Department of Medicine, University of Illinois at Chicago, and Chicago Veterans Administration Medical Center, 60612, USA.
Carroll
R
R
Benya
R V
RV
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D001839:Bombesin / Q000494:pharmacology; D005753:Gastric Mucosa; D015870:Gene Expression; D006801:Humans; D009154:Mutation; D018004:Receptors, Bombesin / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality
D018004:Receptors, Bombesin; D001839:Bombesin