Transfected cholecystokinin receptors mediate growth inhibitory effects on human pancreatic cancer cell lines.
OBJECTIVE
Cholecystokinin (CCK) acting via CCK(A) receptors and gastrin acting via CCK(B) receptors exert trophic effects on a variety of nontransformed tissues. However, their role as hormonal regulators of pancreatic cancer is controversial. The aim of this study was to determine the effects of activation of CCK(A) and CCK(B) receptors on the growth of human pancreatic cancer cells in vitro.


METHODS
Two human pancreatic cell lines MiaPaca-2 and Panc-1 were transfected stably with both CCK receptor subtypes. Effects of CCK on various growth parameters including DNA synthesis, nuclear labeling, and colony formation were evaluated.


RESULTS
Cells expressing either receptor subtype, but not untransfected cells, bound ligand and mobilized Ca2+ in response to CCK. CCK treatment caused a sustained pronounced inhibition of anchorage-independent growth. Similarly, CCK treatment inhibited anchorage-dependent growth. Receptor activation caused a concentration and time-dependent reduction in [3H]thymidine incorporation and nuclear labeling in cells cultured anchored to a plastic substrate. However, these effects on anchorage-dependent growth were transient, suggesting cellular desensitization.


CONCLUSIONS
These data indicate that both CCK receptor subtypes can mediate growth inhibitory responses in pancreatic cancer cell lines and raise the possibility that CCK exerts a predominant growth inhibitory action on human pancreatic cancer cells.
Detjen
K
K
Department of Physiology, University of Michigan, Ann Arbor, USA.
Fenrich
M C
MC
Logsdon
C D
CD
D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011949:Receptors, Cholecystokinin / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011949:Receptors, Cholecystokinin; D004247:DNA; D012844:Sincalide