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Expression of CCK2 receptors in the murine pancreas: proliferation, transdifferentiation of acinar cells, and neoplasia 总被引:8,自引:0,他引:8
Clerc P Leung-Theung-Long S Wang TC Dockray GJ Bouisson M Delisle MB Vaysse N Pradayrol L Fourmy D Dufresne M 《Gastroenterology》2002,122(2):428-437
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. 相似文献
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Death Receptor 5 Internalization Is Required for Lysosomal Permeabilization by TRAIL in Malignant Liver Cell Lines 总被引:1,自引:0,他引:1
Yuko Akazawa Justin L. Mott Steven F. Bronk Nathan W. Werneburg Alisan Kahraman Maria Eugenia Guicciardi Xue Wei Meng Shigeru Kohno Vijay H. Shah Scott H. Kaufmann Mark A. McNiven Gregory J. Gores 《Gastroenterology》2009,136(7):2365-2376
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