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 overexpression of the high-affinity cholecystokinin (CCK) receptor and the novel expression of the gastrin (CCK-B) receptor in the azaserine-induced rat pancreatic carcinoma DSL-6. Since cDNA of both the CCK-A receptor (classical pancreatic CCK receptor) coding region and the CCK-B receptor coding region have recently been cloned and sequenced, we investigated the expression of messenger RNA of these receptors in DSL-6 pancreatic carcinoma. Our results showed that the 32P-labelled cDNA probe of the CCK-A receptor coding region hybridized with an approximately 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 normal rat pancreas. The 32P-labelled cDNA probe of the CCK-B receptor coding region hybridized with an approximately 2.7 kb mRNA from DSL-6 pancreatic carcinoma; no hybridizing mRNA could be identified from normal 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 pancreas. These results further confirm our previous findings based on receptor binding assays. The gene overexpression of the CCK-A receptor and the novel gene expression of the gastrin (CCK-B) receptor may be generated by alterations in gene regulation during carcinogenesis, and may play an important role in promoting tumor growth.
Zhou
W
W
Department of Surgery, University of Cincinnati College of Medicine, OH.
Povoski
S P
SP
Bell
R H
RH
D000818:Animals; D001377:Azaserine; D015152:Blotting, Northern; D002277:Carcinoma / Q000139:chemically induced / Q000737:chemistry*; D008297:Male; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011917:Rats, Inbred Lew; D011949:Receptors, Cholecystokinin / Q000032:analysis*
D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; D001377:Azaserine