Abstracts
1998 Digestive Disease Week

#1071

HUMAN PERIAMPULLARY CARCINOMAS EXPRESS CHOLECYSTO-KININ (CCK-A) RECEPTORS. R.A. Moonka, W. Zhou, and R.H. Bell, Jr. Department of Surgery, University of Washington School of Medicine and VA Medical Center, Seattle, WA.

The peptide hormone cholecystokinin (CCK) is a known tumor promoter in rodent models of pancreatic carcinogenesis (Zhou et al, Cancer Res 53:3925-9, 1993). The relevance of this fact to human carcinogenesis has been questioned because of lack of information about expression of receptors for cholecystokinin on human periampullary malignancies. To determine whether human periampullary malignancies express CCK-A receptor, we isolated RNA from 30 resected specimens of human pancreatic cancer and performed reverse transcription followed by polymerase chain reaction (PCR) with oligonucleotide primers designed to specifically amplify the human CCK-A receptor sequence. RT-PCR product was transferred to nylon membranes and Southern blot analysis performed using a 32P-labelled full-length cDNA probe. CCK-A receptor mRNA was detected in normal human gallbladder (positive control) and in 90.0% (27/30) of human pancreatic carcinomas. Since human operative specimens are made up of numerous cell types, we performed in-situ hybridization to determine if CCK-A receptor expression was localized specifically to tumor cells. A 33P-labelled riboprobe complimentary to the 3' end of the human CCK-A receptor mRNA was generated by in vitro transcription of the CCK-A receptor cDNA in a bacterial plasmid flanked by RNA polymerase promoter sites. This probe was hybridized to paraformaldehyde-fixed frozen sections of 10 human periampullary neoplasms and control tissues. Human gallbladder muscle (positive control) was strongly positive for CCK-A receptor expression. 10 of 10 (100%) of human periampullary malignancies demonstrated CCK-A receptor expression on tumor cells when probed with the antisense riboprobe. No signal was detected on gallbladder or tumor cells with a similar-sized sense riboprobe (negative control). We conclude that human periampullary carcinomas express receptors for cholecystokinin, suggesting that growth effects mediated by CCK may be relevant to the development and growth of periampullary malignancies in man.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.