gastrins and Biliary-Tract-Neoplasms

To investigate the effects of gastrin and cholecystokinin (CCK) and their specific antagonists on the growth of pancreatic and biliary tract cancer cell lines.. Five pancreatic and 6 biliary cancer cell lines with 2 conrtol cells were used in this study. Cell proliferation study was done using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test and direct cell count method. Reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization were performed to examine and quantify the expression of hormonal receptors in these cell lines.. SNU-308 showed a growth stimulating effect by gastrin-17, as did SNU-478 by both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260 for gastrin and L-364, 718 for CCK). Other cell lines did not respond to gastrin or CCK. In RT-PCR, the presence of CCK-A receptor and CCK-B/gastrin receptor mRNA was detected in all biliary and pancreatic cancer cell lines. In slot blot hybridization, compared to the cell lines which did not respond to hormones, those that responded to hormones showed high expression of receptor mRNA.. Gastrin and CCK exert a trophic action on some of the biliary tract cancers.

Topics: Biliary Tract Neoplasms; Cell Count; Cell Division; Cell Line, Tumor; Cholecystokinin; Gastrins; Hormone Antagonists; Humans; Pancreatic Neoplasms; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Reverse Transcriptase Polymerase Chain Reaction; Tetrazolium Salts; Thiazoles

Gastrin is expressed in the gastric antrum and in fetal pancreatic islets but not in adult islets. We have now identified the hepatobiliary tract as another, previously unknown, potential site of gastrin gene expression. Two human gastrin simian virus 40 large tumor antigen (SV40 T antigen) fusion genes containing 1.5 kb of 5' flanking sequence and 10.5 kb that included 5.5 kb upstream, 1.5 kb downstream, and the entire transcribed region were used to generate transgenic mice. Analysis of several transgenic lines, derived from both fusion genes, revealed development of transmissible hepatobiliary tract tumors and pancreatic islet cell tumors. Analysis of each of the tumor cells demonstrates expression of SV40 T antigen but no expression of gastrin. Of the two fusion genes, only the 10.5-kb sequence induces hyperplasia of gastrin-producing cells in the antrum. Analysis of these cells demonstrates expression of SV40 T antigen and gastrin, suggesting that the 10.5-kb sequence is sufficient for gastrin cell hyperplasia in the antrum. These data raise the possibility that gastrin is transiently expressed in the hepatobiliary tract.

Topics: Adenoma, Islet Cell; Animals; Antigens, Viral, Tumor; Biliary Tract Neoplasms; Gastric Mucosa; Gastrins; Hyperplasia; Hypoglycemia; Mice; Mice, Nude; Mice, Transgenic; Pyloric Antrum; Recombinant Fusion Proteins; Simian virus 40