The effect of gastrin on growth of human stomach cancer cells

Ann Surg. 1992 May;215(5):528-34. doi: 10.1097/00000658-199205000-00016.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Calcium / metabolism
  • Gastrins / pharmacology
  • Gastrins / physiology*
  • Hormones / pharmacology
  • Humans
  • In Vitro Techniques
  • Molecular Sequence Data
  • Receptors, Cholecystokinin / antagonists & inhibitors
  • Receptors, Cholecystokinin / drug effects
  • Sincalide / analogs & derivatives
  • Sincalide / pharmacology
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured / drug effects*


  • Gastrins
  • Hormones
  • Receptors, Cholecystokinin
  • JMV 320
  • gastrin 17
  • Sincalide
  • Calcium