| First Author | Clerc P | Year | 2002 |
| Journal | Gastroenterology | Volume | 122 |
| Issue | 2 | Pages | 428-37 |
| PubMed ID | 11832457 | Mgi Jnum | J:74357 |
| Mgi Id | MGI:2158157 | Doi | 10.1053/gast.2002.30984 |
| Citation | Clerc P, et al. (2002) Expression of CCK2 receptors in the murine pancreas: proliferation, transdifferentiation of acinar cells, and neoplasia. Gastroenterology 122(2):428-37 |
| abstractText | BACKGROUND & AIMS: To explore the pancreatic function of CCK2/gastrin receptor, we created ElasCCK2 transgenic mice expressing the human receptor in pancreatic exocrine cells. In previous studies, the transgenic CCK2/gastrin receptor was demonstrated to mediate enzyme release and protein synthesis. We now report results of phenotypic and long-term studies. METHODS: Pancreas was characterized using morphometry and immunohistochemistry. ElasCCK2 mice were crossed with INS-GAS mice expressing gastrin in pancreatic beta cells to achieve continuous stimulation of the CCK2/gastrin receptor. RESULTS: The pancreatic weight of ElasCCK2 mice was increased by 40% and correlated with an increase in the area of exocrine tissue. Alterations in pancreatic histology were apparent from postnatal day 50. Crossing the ElasCCK2 mice with INS-GAS mice resulted in development of morphologic changes in younger animals. Malignant transformation occurred in 3 of 20 homozygous ElasCCK2 mice. Although tumors had different phenotypes, they all developed through an acinar-ductal carcinoma sequence. CONCLUSIONS: Our data show that transgenic expression of a G protein-coupled receptor can lead to cancer. This study also supports a key role of the CCK2/gastrin receptor in the development of pre- and neoplastic lesions of the pancreas. ElasCCK2 mice provide a model for carcinogenesis by transformation and dedifferentiation of acinar cells. |
