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 a re still unknown. We examined the effect of synthetic human gastrin-17 (G-17) on signal-transduction pathways and cell growth using 4 differ ent 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 H CT116 cells, while G-17 stimulated phosphatidylinositol hydrolysis and mobilization of intracellular calcium in HT-29 cells. The groath-regu latory effect of G-17 on these colon cancer cells (stimulatory on LoVo , COLO 320, and HT-29 cells; inhibitory on HCT116 cells) was well corr elated with the effect of G-17 on the signal-transduction pathway in e ach cell line. We further examined the effect of a selective cholecyst okinin-B type receptor antagonist, JMV 320, on G-17-induced signal-tra nsduction pathways and G-17-regulated growth. In each cell line, the e ffect of JMV 320 on G-17-induced signal-transduction pathways was well correlated with that on G-17-regulated growth. G-17 appears to regula te, at least to some extent, growth of human colon cancer cells throug h gastrin receptor-linked signal-transduction pathways that are cell-s pecific.