Gastrin Receptor May Be a Target for Treatment of Colorectal Cancer

In a mouse model of the disease, colonic hyperproliferation was linked to the overexpression of the human protein progastrin, a nonamidated and incompletely processed product of the gastrin gene.

A recent study was undertaken to define the molecular link between progastrin and colonic hyperproliferation. Results published in the August 3, 2009, issue of the Journal of Clinical Investigation revealed a link between progastrin and the cholecystokinin-2 receptor (CCK2R), the primary receptor for cholecystokinin (CCK) and amidated gastrin. CCK is a hormone produced principally by the small intestine in response to the presence of fats, causing contraction of the gallbladder, release of bile, and secretion of pancreatic digestive enzymes. Gastrin is a hormone produced in the stomach, which stimulates gastric acid secretion after a meal.

Investigators from Columbia University (New York, NY, USA) genetically engineered a line of mice that lacked the gene for CCK2R. These animals did not develop colonic hyperproliferation even when progastrin was markedly overexpressed.

The authors concluded that, "These observations indicate that progastrin induces proliferative effects, primarily in colonic progenitor cells, through a CCK2R-dependent pathway. Moreover, our data suggest that CCK2R may be a potential target in the treatment or prevention of colorectal cancer.”

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