AUTORADIOGRAPHIC LOCALIZATION OF CHOLECYSTOKININ (CCK) RECEPTOR EXPRESSION DURING THE DEVELOPMENT OF AZASERINE-INDUCED RAT PANCREATIC-CARCINOMA

The peptide hormone cholecystokinin (CCK) has been shown to stimulate the growth of azaserine-induced preneoplastic nodules in the rat pancr eas. Previously, our laboratory demonstrated by classical binding stud ies that CCK receptors are overexpressed in azaserine-induced rat panc reatic neoplasms. In the present study, we utilized autoradiography to determine the temporal course of this increased receptor binding. Mal e Lewis rats were given azaserine or saline injections and sacrificed at 2, 4, 8, 12, and 18 months of age. Pancreatic tissue was harvested and autoradiography using I-125-labeled- CCK-8 was performed. Densitom etry measurements of azaserine-induced pancreatic nodules, internodula r pancreas, and normal pancreatic tissue (from saline-treated controls ) of each age group were taken with an image analyzer. There was no st atistically significant difference in CCK binding to internodular panc reas and normal pancreas at any age. At 2 months of age, there was no significant increase in CCK binding to azaserine-induced pancreatic no dules. However, at 4, 8, 12, and 18 months of age there was significan tly greater CCK binding to azaserine-induced pancreatic nodules than t o both internodular pancreas and normal pancreas (p < 0.001 for all gr oups). At 18 months of age, one azaserine-treated animal developed a p ancreatic acinar cell carcinoma, which likewise exhibited significantl y greater CCK binding than internodular pancreas or normal pancreas (p < 0.001 for both). These findings demonstrate increased CCK binding i n azaserine-induced preneoplastic pancreatic nodules and pancreatic ac inar cell carcinoma, compatible with our previous demonstration of rec eptor overexpression in these tissues. Increased CCK binding first bec omes apparent by 4 months following exposure to azaserine, These resul ts suggest that overexpression of CCK receptors, located specifically on preneoplastic and neoplastic pancreatic lesions, results in increas ed CCK binding and is involved in the mediation of CCK-stimulated grow th during azaserine-induced pancreatic carcinogenesis.