Effects of gastrin on 3',5'-cyclic adenosine monophosphate, intracellular calcium, and phosphatidylinositol hydrolysis in human colon cancer cells.
Gastrin is a trophic factor for some human colon cancer cells. However, the signal-transduction pathways by which gastrin regulates growth are still unknown. We examined the effect of synthetic human gastrin-17 (G-17) on signal-transduction pathways and cell growth using 4 different human colon cancer cell lines (LoVo, COLO 320, HT-29, and HCT116). G-17 stimulated the production of cyclic AMP in LoVo, COLO 320, and HCT116 cells, while G-17 stimulated phosphatidylinositol hydrolysis and mobilization of intracellular calcium in HT-29 cells. The growth-regulatory effect of G-17 on these colon cancer cells (stimulatory on LoVo, COLO 320, and HT-29 cells; inhibitory on HCT116 cells) was well correlated with the effect of G-17 on the signal-transduction pathway in each cell line. We further examined the effect of a selective cholecystokinin-B type receptor antagonist, JMV 320, on G-17-induced signal-transduction pathways and G-17-regulated growth. In each cell line, the effect of JMV 320 on G-17-induced signal-transduction pathways was well correlated with that on G-17-regulated growth. G-17 appears to regulate, at least to some extent, growth of human colon cancer cells through gastrin receptor-linked signal-transduction pathways that are cell-specific.
Ishizuka
J
J
Department of Surgery, University of Texas Medical Branch, Galveston 77555.
Townsend
C M
CM
Bold
R J
RJ
Martinez
J
J
Rodriguez
M
M
Thompson
J C
JC
D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003110:Colonic Neoplasms; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured
D005755:Gastrins; D006728:Hormones; D010716:Phosphatidylinositols; C013550:gastrin 17; D000242:Cyclic AMP; D002118:Calcium