Gastrin (G-17) and its precursor glycine-extended gastrin (G-17-gly) have b
een shown to be trophic to some gastrointestinal tumors. This in vitro stud
y assessed the effect of G-17, G-17-gly, anti-gastrin antibodies (anti-G-17
), and the CCK-B receptor antagonist PD135,158 on three hepatoma cell lines
(PLC/PRF/5, HepG2 and MCA-RH7777) and an embryonic liver cell line (WRL68)
. The pancreatic adenocarcinoma cell line AR42J was used as a positive cont
rol. G-17 and G-17-gly caused significant proliferation of AR42J and WRL68
cell lines. G-17-gly but not G-17 induced significant proliferation of the
PLC/PRF/5 cell line. Anti-G-17 and PD135,158 significantly inhibited unstim
ulated AR42J and WRL68 cell lines. Anti-G-17 also inhibited the proliferati
ve effects of G-17 and G-17-gly on AR42J, WRL68, and PLC/PRF/5 cell lines,
whereas PD135,158 inhibited the proliferative effect of G-17 only. G-17 and
G-17-gly as well as anti-G-17 and PD135,158 had no effect on HepG2 and MCA
-RH77777 cell lines. It is concluded that G-17-stimulated proliferation is
mediated via the CCK-B receptor and G-17-gly via a separate, as yet unchara
cterized, receptor. There may therefore be a role for gastrin in embryonic
hepatocellular proliferation and perhaps also in the proliferation of some
hepatocellular tumors.