Abstract
Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field.
Highlights
Gastric cancer remains the 2nd leading cause of cancer mortality worldwide, with an overall 5-year survival rate that is less than 25% [1,2]
INS-GAS mice as a model of spontaneous gastric cancer were first described in 2000. These mice were reported to develop atrophic gastritis and intestinal metaplasia, followed by corpus cancer with a high incidence rate, and tumor development was accelerated by H. felis infection, suggesting that this model closely mimicked the clinical course of human gastric carcinogenesis [29]
CCK2R and H2R antagonists synergistically inhibit gastric atrophy and cancer hypergastrinemia increases regeneration of intestinal injury gastrin induces apoptosis and contribute to gastric carcinogenesis identify up- and down-regulating genes among 12,000 cDNA
Summary
Gastric cancer remains the 2nd leading cause of cancer mortality worldwide, with an overall 5-year survival rate that is less than 25% [1,2]. Transgenic mice expressing HPV-16 early region of the bovine keratin 6 gene promoter developed glandular stomach tumors [27] These models did not progress to cancer through the atrophy-metaplasia-dysplasia sequence, as described by Correa [28], nor were they associated with Helicobacter infection or chronic inflammation. These mice were reported to develop atrophic gastritis and intestinal metaplasia, followed by corpus cancer with a high incidence rate, and tumor development was accelerated by H. felis infection, suggesting that this model closely mimicked the clinical course of human gastric carcinogenesis [29] This initial mouse model was followed by the H/K-ATPase-IL-1β transgenic mice, which progressed through the atrophy-metaplasia-dysplasia sequence and validated human genetic data that implicated the IL-1β gene locus as a major risk factor for gastric cancer [30]. We emphasize the impact of comprehensive genomic analysis on new or emerging transgenic mouse models
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
