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 detected the expression of mRNA encoding CCK-A and CCK-B receptors in eight human pancreatic tumour cell lines using reverse transcription-polymerase 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 lines. In addition, Mia PaCa-2 pancreatic cancer cells did not respond to CCK or gastrin in cell proliferation or focal adhesion kinase (FAK) phosphorylation assays. In contrast, mouse NIH3T3 fibroblasts transfected with human CCK-B receptor (NIH3T3CCK-BR) showed increased proliferation and phosphorylation to the peptides. Also, radioligand binding studies indicated that Mia PaCa-2 cells had approximately 12.5-fold less CCK-B receptors than NIH3T3CCK-BR. Our results suggest that in Mia PaCa-2 cells, CCK receptors may not play a crucial role in supporting cell growth.
Mandair
K K
KK
Academic Department of Surgery, Rayne Institute, King's College School of Medicine and Dentistry, London, U.K.
Towner
P
P
Stamford
I F
IF
Morris
J D
JD
Harper
E
E
Benjamin
I S
IS
Tavares
I A
IA
D016475:3T3 Cells; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002455:Cell Division; D005091:Exons; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D011905:Genes, ras; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse