Colorectal cancer, the second most common cause of death from cancer in the United States, is associated with an abnormally high rate of increase in the number of cells lining the colon (colonic hyperproliferation). In mice, overexpression of the human protein progastrin has been shown to cause colonic hyperproliferation and promote colorectal cancer, but the molecular mechanisms underlying this have remained undetermined. In a new study, Timothy Wang and colleagues, at Columbia University Medical Center, New York, have revealed a key link between the protein CCKR2 and progastrin-related colonic hyperproliferation. Initial analysis indicated that the Cck2r gene was upregulated in mice that overexpressed human progastrin. Deletion of this gene in mice that overexpressed human progastrin abolished the colonic hyperproliferation induced by the high levels of human progastrin and markedly diminished the extent of experimentally induced colorectal cancer. As previously published data indicate that levels of progastrin might be elevated in individuals with colorectal cancer, the authors conclude that their study suggests that CCKR2 may be a viable target for the development of drugs to treat or prevent colorectal cancer.
TITLE: Inactivating cholecystokinin-2 receptor inhibits progastrin-dependent colonic crypt fission, proliferation, and colorectal cancer in mice
AUTHOR CONTACT:
Timothy C. Wang
Columbia University Medical Center, New York, New York, USA
Phone: (212) 851-4581; Fax: (212) 851-4590; E-mail: tcw21@columbia.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=38918
Journal
Journal of Clinical Investigation