Expression of CCK2 receptors in the murine pancreas: proliferation, transdifferentiation of acinar cells, and neoplasia
P Clerc, S Leung–Theung–Long, TC Wang… - Gastroenterology, 2002 - Elsevier
P Clerc, S Leung–Theung–Long, TC Wang, GJ Dockray, M Bouisson, MB Delisle, N Vaysse…
Gastroenterology, 2002•ElsevierBackground & Aims: To explore the pancreatic function of CCK2/gastrin receptor, we created
EIasCCK2 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. EIasCCK2 mice were crossed with INS-GAS mice expressing gastrin …
EIasCCK2 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. EIasCCK2 mice were crossed with INS-GAS mice expressing gastrin …
Background & Aims
To explore the pancreatic function of CCK2/gastrin receptor, we created EIasCCK2 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. EIasCCK2 mice were crossed with INS-GAS mice expressing gastrin in pancreatic β cells to achieve continuous stimulation of the CCK2/gastrin receptor.
Results
The pancreatic weight of EIasCCK2 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 EIasCCK2 mice with INS-GAS mice resulted in development of morphologic changes in younger animals. Malignant transformation occurred in 3 of 20 homozygous EIasCCK2 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 preand neoplastic lesions of the pancreas. EIasCCK2 mice provide a model for carcinogenesis by transformation and dedifferentiation of acinar cells.
Elsevier
