CHOLECYSTOKININ RECEPTORS IN HUMAN PANCREATIC-CANCER CELL-LINES

Recent studies have suggested that cholecystokinin (CCK) receptors may play a role in the development and growth of pancreatic cancers. We d etected the expression of mRNA encoding CCK-A and CCK-B receptors in e ight human pancreatic tumour cell lines using reverse transcription-po lymerase chain reaction (RT-PCR), but not by RNase protection assays. The K-ras gene, which can be activated by G-coupled protein receptors such as CCK receptors, was mutated in codon 12 in five of the cell lin es. In addition, Mia PaCa-2 pancreatic cancer cells did not respond to CCK or gastrin in cell proliferation or focal adhesion kinase (FAK) p hosphorylation assays. In contrast, mouse NIH3T3 fibroblasts transfect ed with human CCK-B receptor (NIH3T3CCK-BR) showed increased prolifera tion and phosphorylation to the peptides. Also, radioligand binding st udies indicated that Mia PaCa-2 cells had approximately 12.5-fold less CCK-B receptors than NIH3T3CCK-BR. Our results suggest that in Mia Pa Ca-2 cells, CCK receptors may not play a crucial role in supporting ce ll growth. (C) 1998 Elsevier Science Ltd. All rights reserved.