Povoski S P, Zhou W, Longnecker D S, Bell R H
Department of Surgery, University of Cincinnati College of Medicine, Ohio.
Am J Surg. 1994 Jan;167(1):120-6; discussion 126-7. doi: 10.1016/0002-9610(94)90062-0.
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.
携带弹性蛋白酶I启动子-SV40 T抗原融合基因（ELSV）的转基因小鼠在3至6月龄时会发生胰腺腺泡细胞癌。本研究的目的是确定ELSV转基因小鼠的Tg (Ela-1, SV40E + Ela-1, neo) Bri19品系的胰腺癌和发育异常胰腺是否表达胃泌素（CCK-B）受体。为实现这一目的，我们利用碘125（125I）-胃泌素结合研究、逆转录-聚合酶链反应（RT-PCR）和Southern印迹分析，检测了26周龄雄性ELSV转基因小鼠的胰腺癌、8周龄雄性ELSV转基因小鼠的发育异常胰腺，以及30周龄非转基因雄性小鼠（SJL/J）和8周龄非转基因雄性小鼠（B6SJLF1/J）的正常胰腺。未发现正常非转基因小鼠胰腺有可饱和的胃泌素结合。相反，在pH 6.5、22℃条件下，13例胰腺癌中的9例以及所有5例发育异常胰腺中均检测到可饱和的胃泌素结合。竞争性抑制125I-胃泌素结合试验表明，胃泌素与一类单一的高亲和力受体结合（受体结合亲和力[Kd]为0.11±0.02 nM，胰腺癌的结合容量为1至60 fmol/mg蛋白质；Kd：0.15±0.04 nM，发育异常胰腺的结合容量为1至9 fmol/mg蛋白质）。RT-PCR和Southern印迹分析通过证明胰腺癌和发育异常胰腺中胃泌素（CCK-B）受体mRNA表达，但正常非转基因小鼠胰腺中无mRNA表达，证实了125I-胃泌素结合研究结果。总之，ELSV转基因小鼠的胰腺癌和发育异常胰腺新表达胃泌素（CCK-B）受体。这种表达可能作为致癌多阶段过程的一部分，为腺泡细胞提供生长优势。
