title: Expression of CCK2 receptors in the murine pancreas: proliferation, transdifferentiation of acinar cells, and neoplasia.
abstract: OBJECTIVE
  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.
authors.affiliation: INSERM U531, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Clerc
authors.forename: Stéphane
authors.initials: S
authors.lastname: Leung-Theung-Long
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Dockray
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouisson
authors.forename: Marie-Bernadette
authors.initials: MB
authors.lastname: Delisle
authors.forename: Nicole
authors.initials: N
authors.lastname: Vaysse
authors.forename: Lucien
authors.initials: L
authors.lastname: Pradayrol
authors.forename: Daniel
authors.initials: D
authors.lastname: Fourmy
authors.forename: Marlène
authors.initials: M
authors.lastname: Dufresne
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007515:Islets of Langerhans / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010179:Pancreas / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000235:genetics*
chemical_list: D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin