TUMORS IN HEPATOBILIARY TRACT AND PANCREATIC-ISLET TISSUES OF TRANSGENIC MICE HARBORING GASTRIN SIMIAN VIRUS-40 LARGE TUMOR-ANTIGEN FUSION GENE

Gastrin is expressed in the gastric antrum and in fetal pancreatic isl ets but not in adult islets. We have now identified the hepatobiliary tract as another, previously unknown, potential site of gastrin gene e xpression. 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 ent ire 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 pancreati c 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 e xpression of SV40 T antigen and gastrin, suggesting that the 10.5-kb s equence is sufficient for gastrin cell hyperplasia in the antrum. Thes e data raise the possibility that gastrin is transiently expressed in the hepatobiliary tract.