Novel expression of gastrin (CCK-B) receptors in pancreatic carcinomas and dysplastic pancreas from transgenic mice.
Transgenic mice bearing the elastase I promoter--SV40 T-antigen fusion gene (ELSV) develop pancreatic acinar cell carcinomas by 3 to 6 months of age. The purpose of the study was to determine if pancreatic carcinomas and dysplastic pancreas from the Tg (Ela-1, SV40E + Ela-1, neo) Bri19 strain of ELSV transgenic mice express gastrin (CCK-B) receptors. To accomplish this, we utilized iodine 125 (125I)-gastrin binding studies, reverse transcription-polymerase chain reaction (RT-PCR), and Southern blot analysis to examine pancreatic carcinomas from 26-week-old male ELSV transgenic mice, dysplastic pancreas from 8-week-old male ELSV transgenic mice, and normal pancreas from 30-week-old nontransgenic male mice (SJL/J) and from 8-week-old nontransgenic male mice (B6SJLF1/J). No saturable gastrin binding to normal nontransgenic mouse pancreas was found. In contrast, saturable gastrin binding was detected at pH 6.5, 22 degrees C, in 9 of 13 pancreatic carcinomas and all 5 dysplastic pancreata. Competitive inhibition 125I-gastrin binding assays showed gastrin bound to a single class of high-affinity receptors (receptor binding affinity [Kd] 0.11 +/- 0.02 nM, binding capacities ranging from 1 to 60 fmol/mg protein for pancreatic carcinomas; Kd: 0.15 +/- 0.04 nM, binding capacities ranging from 1 to 9 fmol/mg protein for dysplastic pancreas). RT-PCR and Southern blot analysis confirmed 125I-gastrin binding studies by demonstrating gastrin (CCK-B) receptor mRNA expression in pancreatic carcinomas and dysplastic pancreas but an absence of mRNA expression in normal nontransgenic mouse pancreas. In conclusion, pancreatic carcinomas and dysplastic pancreas in ELSV transgenic mice novelly express gastrin (CCK-B) receptors. This expression may provide a growth advantage to acinar cells as part of the multistage process of carcinogenesis.
Povoski
S P
SP
Department of Surgery, University of Cincinnati College of Medicine, Ohio.
Zhou
W
W
Longnecker
D S
DS
Bell
R H
RH
D000818:Animals; D015139:Blotting, Southern; D018267:Carcinoma, Acinar Cell / Q000737:chemistry*; D005755:Gastrins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000002:abnormalities* / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000032:analysis*
D005755:Gastrins; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin