The effect of gastrin on growth of human stomach cancer cells.
Gastrin is known as a trophic factor for some stomach and colorectal cancer cells; however, the roles of gastrin receptors and the intracellular signal transduction pathways by which gastrin regulates cell growth are still unknown. The authors examined the effect of synthetic human gastrin-17 on growth of human stomach cancer cells (the parent line, AGS-P, and two different clones, AGS-10 and AGS-12), which were established (and have been maintained) in our laboratory. Gastrin stimulated growth of AGS-P and AGS-10 cells, which have gastrin receptors, in a dose-dependent fashion. A highly selective gastrin receptor antagonist, JMV 320, inhibited the growth-stimulatory effect of gastrin on AGS-P cells in a dose-dependent fashion. Concentrations of gastrin (10(-8) to 10(-6) M), which stimulated growth of AGS-P cells, did not affect either cyclic adenosine monophosphate production or phosphatidylinositol hydrolysis. Gastrin (10(-11) to 10(-5) M) mobilized calcium from the intracellular organelles to increases intracellular calcium level in AGS-P cells. The AGS-12 clone has no gastrin receptors, and gastrin did not affect growth or mobilization of intracellular calcium in these cells. Our findings indicate that gastrin stimulates growth of AGS cells through a mechanism that involves binding to specific gastrin receptors that are linked to the system for mobilization of intracellular calcium.
Ishizuka
J
J
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Martinez
J
J
Townsend
C M
CM
Thompson
J C
JC
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology / Q000502:physiology*; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D005755:Gastrins; D006728:Hormones; D011949:Receptors, Cholecystokinin; C075380:JMV 320; C013550:gastrin 17; D012844:Sincalide; D002118:Calcium