The gastrin receptor promotes pancreatic growth in transgenic mice.
BACKGROUND
We demonstrated previously, in two different rodent models of pancreatic cancer, that the gastrin receptor is present on malignant pancreatic tumors in spite of the fact that the normal adult rat and mouse pancreas does not express gastrin receptors.


OBJECTIVE
To determine whether gastrin receptors mediate pancreatic growth or promote carcinogenesis or both, we created a transgenic mouse that constitutively expresses gastrin receptors in the exocrine pancreas. The transgene construct contained the full-length rat gastrin receptor cDNA sequence under the control of the rat elastase promoter.


RESULTS
Receptor presence and function on exocrine pancreatic tissue of transgenic but not control mice were confirmed by (125)I-gastrin-I binding studies and by gastrin stimulation of intracellular calcium release. Eighteen-month-old transgenic animals had larger pancreas-to-body weight ratios than their nontransgenic littermate controls (p < 0.001 for females; p < 0.01 for males); however, histopathologic examination revealed no neoplasms or other abnormalities.


CONCLUSIONS
In both female and male transgenic mice, the expression of the gastrin receptor in the exocrine pancreas is associated with a significant increase in pancreas weight, but it does not appear to promote the development of spontaneous pancreatic tumors.
Yen
Tina W F
TW
Surgical Service, Veterans Administration Puget Sound Health Care System, University of Washington School of Medicine, Seattle, Washington, U.S.A.
Sandgren
Eric P
EP
Liggitt
H Denny
HD
Palmiter
Richard D
RD
Zhou
Weigong
W
Hinds
Thomas R
TR
Grippo
Paul J
PJ
McDonald
Jerome M
JM
Robinson
Linda M
LM
Bell
Richard H
RH
D000230:Adenocarcinoma / Q000503:physiopathology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000254:growth & development* / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000503:physiopathology; D010641:Phenotype; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000235:genetics* / Q000378:metabolism*
D005755:Gastrins; D007457:Iodine Radioisotopes; D011949:Receptors, Cholecystokinin; C036227:gastrin I; D002118:Calcium