| First Author | Cobb S | Year | 2002 |
| Journal | Gastroenterology | Volume | 123 |
| Issue | 2 | Pages | 516-30 |
| PubMed ID | 12145805 | Mgi Jnum | J:77985 |
| Mgi Id | MGI:2183018 | Doi | 10.1053/gast.2002.34754 |
| Citation | Cobb S, et al. (2002) Deletion of functional gastrin gene markedly increases colon carcinogenesis in response to azoxymethane in mice. Gastroenterology 123(2):516-30 |
| abstractText | BACKGROUND & AIMS: We recently reported that transgenic mice overexpressing progastrin were at a higher risk for developing colon cancers in response to azoxymethane (AOM), whereas mice overexpressing gastrin-17 were at a reduced risk. To examine further the role of gastrins in colon carcinogenesis, we generated gastrin gene knockout mice (GAS-KO). METHODS: The height and proliferative index (PI) of colonic crypts were similar in GAS-KO and wild-type (WT) mice, suggesting that the absence of gastrins in GAS-KO mice did not significantly affect the growth of colonic mucosa. GAS-KO and WT mice were treated with AOM for 3-4 weeks; control mice received saline. RESULTS: Colonic proliferation in response to AOM was significantly increased in GAS-KO vs. WT mice. Aberrant crypt foci (ACFs) were similarly increased significantly by approximately 2-5-fold in GAS-KO vs. WT mice after 2 weeks of AOM treatment. Female GAS-KO mice developed adenomas (Ads) and adenocarcinomas (AdCAs) at earlier times ( approximately 10 months) than the male GAS-KO mice and the male and female WT mice ( approximately 12 months). The total numbers of Ads and AdCAs were significantly higher in GAS-KO than in WT mice. CONCLUSIONS: These results suggest the novel possibility that loss of gastrin expression (and hence amidated gastrins) significantly increases susceptibility to colon carcinogenesis in response to AOM. Previous studies with FVB/N transgenic mice similarly suggested a protective role of amidated gastrins against colon carcinogenesis, which supports the present findings of an increase in colon carcinogenesis in GAS-KO mice lacking normal physiological levels of amidated gastrins. |
