GASTRIN RECEPTOR EXPRESSION DURING AZASERINE-INDUCED RAT PANCREATIC CARCINOGENESIS

The hormone gastrin is thought to stimulate the growth of certain panc reatic carcinoma cell lines. We have previously detected the presence of the gastrin receptor in rat pancreatic carcinoma cell lines but not in normal rat pancreas. We had not, however, previously demonstrated that gastrin receptor is expressed in pancreatic carcinomas developing in the rat in vivo. Therefore, in the present study, we examined rat pancreatic tissue at various stages in azaserine-induced pancreatic ca rcinogenesis for gastrin binding and for the presence of gastrin recep tor mRNA to determine the temporal expression pattern of the gastrin r eceptor during the in vivo development of pancreatic cancer. Autoradio graphy of pancreatic tissue using I-125-gastrin-17-I from all azaserin e-treated and control animals at 2, 4, 8, and 12 months of age demonst rated no specific gastrin binding. At 18 months of age, normal pancrea s, azaserine-induced premalignant pancreatic nodules, and internodular pancreas demonstrated no specific gastrin binding. One of three azase rine-treated animals developed an area of pancreatic acinar cell carci noma at 18 months of age which exhibited significant specific gastrin binding of 141.8 +/- 32.8 fmole/gm of tissue. Southern blot analysis o f pancreatic RNA isolated from animals at 12 months of age revealed no gastrin receptor mRNA; however, by 18 months of age, gastrin receptor mRNA was present in all azaserine-treated animals but absent in contr ol animals. In summary, specific gastrin binding is present in in vivo azaserine-induced pancreatic acinar cell carcinoma but absent in norm al pancreas and azaserine-induced premalignant pancreatic nodules, Gas trin receptor mRNA is first expressed in azaserine-treated rat pancrea s at some point between 12 and 18 months of age. These results demonst rate that expression of gastrin receptor is altered in azaserine-treat ed rat pancreas and may play a role in the development of pancreatic c ancer. (C) 1996 Academic Press, Inc.