Role of gastrin-peptides in Barrett's and colorectal carcinogenesis

Table 2 Experimental studies in animal models exploring the impact of increased levels of gastrin peptides

Ref.	Animal model	Alteration on gastrin peptides levels	Hypergastrinemia effects
Cobb et al[2]	Fabp-wt mice; Fabp-mt mice	Fabp-wt mice express human PG in intestinal mucosa and Fabp-mt mice express a mutated form of human PG; Both mice show PG expression at similar levels as seen in hypergastrinemia	Mice overexpressing human PG (either the wild-type and the mutated form) are more likely to develop colonic tumors in response to AOM
Wang et al[5]	INS-GAS mice; hGAS mice	INS-GAS mice overexpress human amidated gastrin in the pancreatic islands; hGAS mice overexpress human PG in the liver	Both forms of gastrin showed similar proliferative effects on normal colonic mucosa
Havu et al[34]	Sprague-Dawley rats treated with ranitidine (2g/kg per day)	Rats showed a 3-fold increase in plasma gastrin levels	19/100 rats developed ECL carcinoids while no carcinoma was found in control animals
Watson et al[43]	APCMin+/- mice (model of multiple intestinal neoplasia) treated with omeprazole (75 mg/kg in a single oral dose)	Omeprazole increased only amidated gastrin plasma levels	PPI-induced hypergastrinemia reduced mice survival; Hypergastrinemia increased colonic adenomas proliferation; Hypergastrinemia did not increase the incidence of intestinal tumors
Ferrand et al[90]	MTI/G-Gly mice; hGAS mice	MTI/G-Gly mice overexpress human G-Gly throughout the gastrointestinal tract; hGAS mice overexpress human PG in the liver	Both G-Gly and PG strongly up-regulate Src, JAK2 and STAT3 activation; PG produced significantly great ERK and Akt pathways activation and TGF-α overexpression
Koh et al[95]	MTI/G-Gly mice	MTI/G-Gly mice overexpress human G-Gly throughout the gastrointestinal tract	Goblet cells hyperplasia and colonic hyperproliferation; Hypergastrinemia did not increase the incidence of GI tumors, but 3/10 mice developed bronchoalveolar carcinoma
Ottewell et al[98]	G-/-hg+/+ mice; G-/-hg-/- mice	G-/-hg+/+ mice express human PG and no murine gastrin; G-/-hg-/- mice do not express any forms of gastrin	PG increased colonic proliferation; PG exerts mitotic effects on colonic epithelia but does not seem to affect the small intestine epithelia

PG: Progastrin; AOM: Azoxymethane; ECL: Enterochromaffin-like cells; PPI: Proton pump inhibitors; G-Gly: Glycine-extended gastrins; JAK2: Janus-activated kinase 2; STAT3: Signal transducer and activator of transcription 3; ERK: Extracellular-signal regulated kinase; Akt: Protein kinase B; TGF-α: Transforming growth factor-alpha; GI: Gastrointestinal.