Gastrin is an essential cofactor for helicobacter-associated gastric corpus carcinogenesis in C57BL/6 mice.
We have previously described a synergistic interaction between hypergastrinemia and Helicobacter felis infection on gastric corpus carcinogenesis in FVB/N mice housed under specific-pathogen-free conditions. However, gastrin-deficient (GAS-KO) mice on a mixed C57BL/6/129Sv genetic background maintained in conventional housing were reported to develop spontaneous gastric antral tumors. Therefore, we investigated the role of gastrin in Helicobacter-associated gastric carcinogenesis in H. felis-infected mice on a uniform C57BL/6 background housed in specific-pathogen-free conditions. Hypergastrinemic transgenic (INS-GAS) mice, GAS-KO mice, and C57BL/6 wild-type mice were infected with H. felis for either 12 or 18 months. At 12 months postinfection, INS-GAS mice had mild corpus dysplasia, while B6 wild-type mice had either severe gastritis or metaplasia, and GAS-KO mice had only mild to moderate gastritis. At 18 months postinfection, both INS-GAS and B6 wild-type mice had both severe atrophic gastritis and corpus dysplasia, while GAS-KO mice had severe gastritis with mild gastric atrophy, but no corpus dysplasia. In contrast, both GAS-KO and B6 wild-type mice had mild to moderate antral dysplasia, while INS-GAS mice did not. H. felis antral colonization remained stable over time among the three groups of mice. These results point to a distinct effect of gastrin on carcinogenesis of both the gastric corpus and antrum, suggesting that gastrin is an essential cofactor for gastric corpus carcinogenesis in C57BL/6 mice.
Takaishi
Shigeo
S
Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York, USA.
Tu
Shuiping
S
Dubeykovskaya
Zinaida A
ZA
Whary
Mark T
MT
Muthupalani
Sureshkumar
S
Rickman
Barry H
BH
Rogers
Arlin B
AB
Lertkowit
Nantaporn
N
Varro
Andrea
A
Fox
James G
JG
Wang
Timothy C
TC
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005755:Gastrins / Q000235:genetics / Q000378:metabolism*; D005756:Gastritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D044922:Helicobacter felis; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines; D005755:Gastrins; D012333:RNA, Messenger