GASTRIN-17 AND G17-GLY INDUCE PROLIFERATION THROUGH ACTIVATION OF CCKB GASTRIN RECEPTOR IN LOVO CELLS/

Background and methods. - Recent studies suggest that glycine-extended gastrin (G17-gly) stimulates in vitro proliferation of the pancreatic cell line AR4-2J, through selective receptors distinct from the CCK-B /G-receptor mediating the effects of amidated gastrin (G17). The aims of our study were to examine the effects of G17 and G17-gly on the gro wth of the colorectal cancer cell line LoVo and to determine the recep tor involved by using selective receptor-antagonist. Results. - Both G 17 and G17-gly stimulated [3H]-thymidine incorporation in a concentrat ion-dependent fashion. Maximal stimulation (153 +/- 18 % and 166 +/- 1 7 % of control, p < 0.01) was achieved with IO nM G17 and 100 nM G17-g ly respectively! These stimulations were fully prevented by the presen ce of 10 pM YM022, a G/CCK B receptor-antagonist, but unaffected by L3 64,718, a CCK A receptor-antagonist. Basal growth of LoVo cells was in hibited by YM022 and stimulated by L364, 718, CCK A and G/CCK B recept ors mRNA were detected in the cells. Gastrin immunoreactivity was dete cted in the cells (16 pM) and in the extracellular medium (4.5 pM). Co nclusion. - Both G17 and G17-gly stimulate LoVo cells growth through t he activation of a gastrin/CCK B receptor The evidence for secreted ga strin and CCK A and B receptors mRNA may further suggest the existence of an autocrine loop involving a stimulatory gastrin/CCK B receptor.