Effect of gastrin and anti-gastrin antibodies on proliferation of hepatocyte cell lines.
Gastrin (G-17) and its precursor glycine-extended gastrin (G-17-gly) have been shown to be trophic to some gastrointestinal tumors. This in vitro study 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 control. 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 unstimulated AR42J and WRL68 cell lines. Anti-G-17 also inhibited the proliferative 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 uncharacterized, receptor. There may therefore be a role for gastrin in embryonic hepatocellular proliferation and perhaps also in the proliferation of some hepatocellular tumors.
Caplin
M
M
Department of Medicine, Royal Free Hospital School, London, UK.
Khan
K
K
Grimes
S
S
Michaeli
D
D
Savage
K
K
Pounder
R
R
Dhillon
A
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005755:Gastrins / Q000276:immunology* / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects
D000906:Antibodies; D005755:Gastrins; D007211:Indoles; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C086854:glycine-extended gastrin 17; C065600:PD 135158; C013550:gastrin 17; D008536:Meglumine