Smith J P, Shih A, Wu Y, McLaughlin P J, Zagon I S
Department of Medicine Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Am J Physiol. 1996 May;270(5 Pt 2):R1078-84. doi: 10.1152/ajpregu.1996.270.5.R1078.
The gastrointestinal peptides gastrin and cholecystokinin (CCK) stimulate growth of human pancreatic cancer through a CCK-B/gastrin- like receptor. In the present study we evaluated whether growth of human pancreatic cancer is endogenously regulated by gastrin. Immunohistomical examination of BxPC-3 cells and tumor xenografts revealed specifc gastrin immunoreactivity. Gastrin was detected by radioimmunoassay in pancreatic cancer cell extracts and in pancreatic cancer cell extracts and in the growth media. With use of reverse-transcriptase polymerase chain reaction gastrin gene expression was detected in both cultured BxPC-3 cancer cells and transplanted tumors, as well as seven addition human pancreatic cancer cell lines. Growth of BxPC-3 human pancreatic cancer cell in serum-free medium was inhibited by the addition of the CCK-B/gastrin receptor antagonist L-365,260, and gastrin treatment reversed the inhibitory effect of the antagonist. A selective gastrin antibody (Ab repressed growth of BxPC-3 cells. Gastrin immunoreactivity was detected in fresh human pancreatic cancer specimens but not in normal human pancreatic tissue. These data provide the first evidence that growth of a human pancreatic cancer is tonically stimulated by the autocrine production of gastrin. Evidence for the ubiquity of this system was provided by the detection of gastrin gene expression in multiple human pancreatic cancer cell lines and detection of gastrin in cell lines and fresh pancreatic tumors.
胃肠肽胃泌素和胆囊收缩素（CCK）通过CCK-B/胃泌素样受体刺激人胰腺癌生长。在本研究中，我们评估了人胰腺癌的生长是否受胃泌素的内源性调节。对BxPC-3细胞和肿瘤异种移植物进行免疫组织学检查，发现有特异性胃泌素免疫反应性。通过放射免疫测定法在胰腺癌细胞提取物、生长培养基中检测到胃泌素。利用逆转录聚合酶链反应，在培养的BxPC-3癌细胞、移植瘤以及另外七种人胰腺癌细胞系中均检测到胃泌素基因表达。在无血清培养基中添加CCK-B/胃泌素受体拮抗剂L-365,260可抑制BxPC-3人胰腺癌细胞生长，而胃泌素处理可逆转该拮抗剂的抑制作用。一种选择性胃泌素抗体（Ab）可抑制BxPC-3细胞生长。在新鲜人胰腺癌标本中检测到胃泌素免疫反应性，但在正常人胰腺组织中未检测到。这些数据首次证明，人胰腺癌的生长受到胃泌素自分泌产生的持续刺激。在多种人胰腺癌细胞系中检测到胃泌素基因表达，以及在细胞系和新鲜胰腺肿瘤中检测到胃泌素，为该系统的普遍性提供了证据。
