Journal article

Inactivating cholecystokinin-2 receptor inhibits progastrin-dependent colonic crypt fission, proliferation, and colorectal cancer in mice

Guangchun Jin, Vigneshwaran Ramanathan, Michael Quante, Gwang Ho Baik, Xiangdong Yang, Sophie SW Wang, Shuiping Tu, Shanisha AK Gordon, David Mark Pritchard, Andrea Varro, Arthur Shulkes, Timothy C Wang

JOURNAL OF CLINICAL INVESTIGATION | AMER SOC CLINICAL INVESTIGATION INC | Published : 2009

Abstract

Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely processed product of the gastrin gene, has been shown to induce colonic hyperproliferation and promote colorectal cancer in mice, but the mechanism of pathogenesis has not been defined. Cholecystokinin-2 receptor (CCK2R) is the primary receptor for cholecystokinin (CCK) and amidated gastrin. Here, we show that Cck2r was expressed in murine colonic crypts and upregulated in the transgenic mice that overexpress human progastrin. Murine deletion of Cck2r abrogated progastrin-dependent incr..

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University of Melbourne Researchers

Grants

Awarded by NIH


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Awarded by Medical Research Council


Funding Acknowledgements

This work was supported by the NIH through grant S R01 DK052778 (to Timothy C. Wang), the North West Cancer Research fund (to David Mark Pritchard and Andrea Varro), the National Health and Medical Research Council of Australia fund (to Arthur Shulkes), and a fellowship grant of Mildred Scheel Stiftung (Deutsche Krebshilfe; to Michael Quante).