OVEREXPRESSION OF MESSENGER-RNA FOR CHOLECYSTOKININ-A RECEPTOR AND NOVEL EXPRESSION OF MESSENGER-RNA FOR GASTRIN (CHOLECYSTOKININ-B) RECEPTOR IN AZASERINE-INDUCED RAT PANCREATIC-CARCINOMA

Using receptor binding assays, we have previously demonstrated the ove rexpression of the high-affinity cholecystokinin (CCK) receptor and th e novel expression of the gastrin (CCK-B) receptor in the azaserine-in duced rat pancreatic carcinoma DSL-6. Since cDNA of both the CCK-A rec eptor (classical pancreatic CCK receptor) coding region and the CCK-B receptor coding region have recently been cloned and sequenced, we inv estigated the expression of messenger RNA of these receptors in DSL-6 pancreatic carcinoma. Our results showed that the P-32-labelled cDNA p robe of the CCK-A receptor coding region hybridized with an almost-equ al-to 2.7 kb mRNA from both DSL-6 pancreatic carcinoma and normal rat pancreas. However, the relative expression of the CCK-A receptor mRNA in DSL-6 pancreatic carcinoma was approximately 8-fold of that in norm al rat pancreas. The P-32-labelled cDNA probe of the CCK-B receptor co ding region hybridized with an almost-equal-to 2.7 kb mRNA from DSL-6 pancreatic carcinoma; no hybridizing mRNA could be identified from nor mal rat pancreas. In summary, the CCK-A receptor mRNA is overexpressed approximately 8-fold and the gastrin (CCK-B) receptor mRNA is novelly expressed in DSL-6 pancreatic carcinoma as compared to normal rat pan creas. These results further confirm our previous findings based on re ceptor binding assays. The gene overexpression of the CCK-A receptor a nd the novel gene expression of the gastrin (CCK-B) receptor may be ge nerated by alterations in gene regulation during carcinogenesis, and m ay play an important role in promoting tumor growth.