Reference SummaryWatson SA, Cancer Res 2001 Jan 15;61(2):625-31

Title

Hypergastrinemia promotes adenoma progression in the APC(Min-/+) mouse model of familial adenomatous polyposis.

Authors

Watson SA; Smith AM

Journal

Cancer Res

Volume

Issue

Year

2001

Pages

625-31

Abstract

Serum hypergastrinemia promotes the growth of colorectal adenocarcinoma. Some colorectal adenomas express cholecystokinin B/gastrin receptor mRNA, and thus hypergastrinemia may increase progression through the adenoma-carcinoma sequence. This was investigated in the multiple intestinal neoplasia APC(Min-/+) mouse. Serum gastrin levels in APC(Min-/+) mice were elevated 5-6-fold by oral administration of omeprazole (75 mg/kg). Terminal tumor burden was monitored by onset of anemia. A labeling index was generated by immunohistochemical detection of bromodeoxyuridine incorporation. Serum gastrin was neutralized by antigastrin antibodies raised in situ by use of a gastrin immunogen, Gastrimmune. Hypergastrinemia resulted in reduced survival of the APC(Min-/+) mice from a median survival of 13 weeks in the controls to 10 weeks following omeprazole treatment (P < 0.00001, log-rank test). The labeling indices of adenomas from the small and large intestines of omeprazole-treated mice were increased 35 and 29%, respectively (P < 0.05 and P < 0.025, respectively). Gastrimmune immunization reversed both the survival effect and the increased proliferation resulting from serum hypergastrinemia. Hypergastrinemia may promote the progression of existing premalignant colonic lesions by increasing proliferation. Clinical investigations should determine whether this occurs in the human scenario, considering the widespread use of proton pump inhibitors.

Links

J:67449 – MGI References
11212260 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
C57BL/6-Apc^Min/+	Mice terminated 12 days after onset of anemia. Mice were bred within the Cancer Studies Unit at the University of Nottingham. Heterozygous males were bred with wild type C57BL/6 females. Omeprazole treatment yielded median serum omeprazole levels of 5.82 microg/ml.

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency
C57BL/6-Apc^Min/+	Intestine - Large Intestine carcinoma - polypoid		Intestine - Large Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Large Intestine carcinoma - polypoid	omeprazole	Intestine - Large Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Large Intestine tumor		Intestine - Large Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Large Intestine tumor	omeprazole	Intestine - Large Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Large Intestine tumor	omeprazole rat Gastrimmune	Intestine - Large Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Large Intestine tumor	rat Gastrimmune	Intestine - Large Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Small Intestine tumor		Intestine - Small Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Small Intestine tumor	omeprazole	Intestine - Small Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Small Intestine tumor	omeprazole rat Gastrimmune	Intestine - Small Intestine	observed
C57BL/6-Apc^Min/+	Intestine - Small Intestine tumor	rat Gastrimmune	Intestine - Small Intestine	observed