Montag A G, Oka T, Baek K H, Choi C S, Jay G, Agarwal K
Department of Pathology, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6696-700. doi: 10.1073/pnas.90.14.6696.
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.
胃泌素在胃窦和胎儿胰岛中表达，但在成年胰岛中不表达。我们现已确定肝胆系统是胃泌素基因表达的另一个此前未知的潜在部位。两个包含1.5 kb 5'侧翼序列和10.5 kb（包括上游5.5 kb、下游1.5 kb以及整个转录区域）的人胃泌素猿猴病毒40大T抗原（SV40 T抗原）融合基因被用于生成转基因小鼠。对源自这两个融合基因的多个转基因品系的分析显示，出现了可传播的肝胆系统肿瘤和胰岛细胞瘤。对每个肿瘤细胞的分析表明，有SV40 T抗原的表达，但没有胃泌素的表达。在这两个融合基因中，只有10.5 kb的序列可诱导胃窦中产生胃泌素的细胞增生。对这些细胞的分析表明，有SV40 T抗原和胃泌素的表达，这表明10.5 kb的序列足以使胃窦中的胃泌素细胞增生。这些数据增加了胃泌素在肝胆系统中短暂表达的可能性。
