Differential expression of gastrin, cholecystokinin-A and cholecystokinin-B receptor mRNA in human pancreatic cancer cell lines
2001 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 36, no 7, 738-743 p.Article in journal (Refereed) Published
Background: It has been assumed that gastrin stimulates the growth of pancreatic cancer in an autocrine way through co-expression of gastrin and the cholecystokinin-B receptor (CCK-BR). However, pancreatic cancer cell lines established directly from patients have revealed a great heterogeneity in cell proliferation when exposed to CCK, gastrin and their receptor antagonists. The aim of this study was therefore to examine co-expression of CCK-A and CCK-B receptor (CCK-AR and CCK-BR), and gastrin mRNA as well as the secretion of CCK and gastrin peptides in these cell lines. Methods: Fourteen cell lines were established from primary pancreatic cancers or their metastases. Total RNA was isolated from the cell lines and reverse-transcribed into single-stranded cDNA. A PCR technique based on Tag polymerase-antibody interaction and CCK-AR, CCK-BR and gastrin-specific primers, followed by Southern blot analysis, were the methods used. The incubation mediums were analysed for the presence of secreted CCK/proCCK and gastrin/progastrin peptides by specific radioimmunoassays (RIA). Results: By means of nested Reverse-Transcribed Polymerase Chain Reaction (nested RT-PCR), combined with Southern blot analysis of the PCR amplified products, CCK-AR and gastrin mRNA co-expression was detected in cell Lines LPC-6p and LPC-10m, whereas CCK-BR and gastrin mRNA could be detected in cell lines LPC-8p and LPC-12m. A low level of secreted CCK peptides was detected in cell line LPC-6p. which also expressed CCK-AR mRNA. In no other cases were CCK or gastrin peptides detected in the cell culture mediums. Conclusion: The lack of CCK-BR and gastrin mRNA co-expression, and not detectable levels of secreted CCK and gastrin in culture media, does not lend support to the hypothesis that concomitant gene-expression of CCK receptors and gastrin or CCK are essential to maintaining pancreatic cancer cell proliferation.
Place, publisher, year, edition, pages
2001. Vol. 36, no 7, 738-743 p.
cholecystokinin (CCK), CCK-A receptor, CCK-B receptor, gastrin, gene expression, pancreatic cancer
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-49227OAI: oai:DiVA.org:liu-49227DiVA: diva2:270123