CHOLECYSTOKININ RECEPTOR CHARACTERIZATION AND CHOLECYSTOKININ-A RECEPTOR MESSENGER-RNA EXPRESSION IN TRANSGENIC MOUSE PANCREATIC CARCINOMASAND DYSPLASTIC PANCREAS

Transgenic mice bearing the rat elastase I promoter - SV40 T-antigen ( ELSV) fusion gene develop pancreatic acinar cell carcinomas by 3-6 mon ths of age. In other animal models of pancreatic cancer, cholecystokin in (CCK) has been shown to be a tumor promoter. Therefore, we characte rized CCK binding properties and CCK-A receptor mRNA expression in pan creatic carcinomas and dysplastic pancreata from the Tg(Ela-1, SV40E Ela-1, neo)Bri19 strain of ELSV transgenic mice. To accomplish this, we utilized I-125-Bolton-Hunter-labeled-cholecystokinin octapeptide (I -125-BH-CCK-8) binding studies, reverse transcription-polymerase chain reaction (RT-PCR), and Southern blot analysis to examine pancreatic c arcinomas from 26-week-old male ELSV transgenic mice, dysplastic pancr eata from 8-week-old male ELSV transgenic mice, and normal pancreas fr om 30-week-old nontransgenic male mice (SJL/J) and 8-week-old nontrans genic male mice (B6SJLF(1)/J). Optimal saturable CCK-8 binding was det ected at pH 6.5, 22 degrees C. Competitive inhibition I-125-BH-CCK-8 b inding assays performed on all four mouse pancreatic tissues showed th at CCK-8 bound to two classes of CCK binding sites: a high affinity, l ower capacity CCK binding site and a low affinity, higher capacity CCK binding site. RT-PCR and Southern blot analysis confirmed the I-125-B H-CCK-8 binding studies by demonstrating CCK-A receptor mRNA expressio n in the ELSV transgenic pancreatic carcinomas and dysplastic pancreas , as well as in normal nontransgenic mouse pancreas. In conclusion, pa ncreatic carcinomas and dysplastic pancreas from ELSV transgenic mice and normal nontransgenic mouse pancreas all bind I-125-BH-CCK-8 and ex press mRNA for the CCK-A receptor. In contrast to chemically-induced p ancreatic tumors in the rat, ELSV transgenic mouse pancreatic tumors d o not appear to significantly overexpress CCK-A receptors.