Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin.
OBJECTIVE
Gastrin (G-17) stimulates the growth of certain gastric and colon cancers mostly through gastrin/cholecystokinin (CCK)-B receptors. Glycine-extended gastrin (Gly-G) stimulates growth of a rat pancreatic acinar cell line; however, the effect of Gly-G on human gastric cancers is not known. The purpose of this study was to characterize the trophic effect of G-17 and Gly-G on two human gastric cancer cell lines, AGS and SIIA.


METHODS
Binding analyses were performed, and cell growth was assessed by counting cells over a time course.


RESULTS
G-17 stimulated growth of both AGS and SIIA cells. In AGS cells, gastrin/CCK-B receptor antagonists inhibited the effect of G-17 and competitively antagonized 125I-G-17 binding, whereas the CCK-preferring (CCK-A) receptor antagonists had no effect. In contrast, CCK-A receptor antagonists inhibited the stimulatory effect of G-17 in SIIA cells, whereas CCK-B receptor antagonists had no effect. Gly-G stimulated the growth of AGS and SIIA cells; neither the CCK-B nor the CCK-A receptor antagonists blocked this effect.


CONCLUSIONS
G-17 stimulates proliferation of AGS cells through the CCK-B receptor; however, G-17-mediated growth of SIIA acts through a CCK-A-like receptor. Furthermore, Gly-G stimulates growth of human gastric cancer cell lines, possibly through a receptor other than the CCK-B or CCK-A receptor.
Iwase
K
K
Department of Surgery, University of Texas Medical Branch, Galveston, USA.
Evers
B M
BM
Hellmich
M R
MR
Guo
Y S
YS
Higashide
S
S
Kim
H J
HJ
Townsend
C M
CM
D002455:Cell Division / Q000187:drug effects; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology*; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005755:Gastrins; D011498:Protein Precursors; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C086854:glycine-extended gastrin 17; C013706:big gastrin