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TISSUE-SPECIFIC STEM CELLS

Identification of a Novel Putative Gastrointestinal Stem Cell and Adenoma Stem Cell Marker, Doublecortin and CaM Kinase-Like-1, Following Radiation Injury and in Adenomatous Polyposis Coli/Multiple Intestinal Neoplasia Mice

Departments of ^aMedicine and
^dCell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA;
^bDepartment of Internal Medicine, Division of Gastroenterology, and
^cDepartment of Radiation Oncology, Radiation and Cancer Biology Division, Washington University School of Medicine, St. Louis, Missouri, USA

Key Words. Stem cell marker • Doublecortin and CaM kinase-like-1 • Adenoma stem cell marker • Gamma irradiation • Gastrointestinal cancer • Adenomatous polyposis coli/multiple intestinal neoplasia mice

Correspondence: Courtney W. Houchen, M.D., Department of Medicine, University of Oklahoma Health Sciences Center, 920 Stanton L. Young Boulevard, WP 1360, Oklahoma City, Oklahoma 73104, USA. Telephone: 405-271-2175; Fax: 405-271-5450; e-mail: Courtney-houchen{at}ouhsc.edu

Received July 31, 2007; accepted for publication November 19, 2007.
First published online in STEM CELLS EXPRESS   November 29, 2007.



In the gut, tumorigenesis arises from intestinal or colonic crypt stem cells. Currently, no definitive markers exist that reliably identify gut stem cells. Here, we used the putative stem cell marker doublecortin and CaM kinase-like-1 (DCAMKL-1) to examine radiation-induced stem cell apoptosis and adenomatous polyposis coli (APC)/multiple intestinal neoplasia (min) mice to determine the effects of APC mutation on DCAMKL-1 expression. Immunoreactive DCAMKL-1 staining was demonstrated in the intestinal stem cell zone. Furthermore, we observed apoptosis of the cells negative for DCAMKL-1 at 6 hours. We found DNA damage in all the cells in the crypt region, including the DCAMKL-1-positive cells. We also observed stem cell apoptosis and mitotic DCAMKL-1-expressing cells 24 hours after irradiation. Moreover, in APC/min mice, DCAMKL-1-expressing cells were negative for proliferating cell nuclear antigen and nuclear β-catenin in normal-appearing intestine. However, β-catenin was nuclear in DCAMKL-1-positive cells in adenomas. Thus, nuclear translocation of β-catenin distinguishes normal and adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing novel chemotherapeutic agents.

Disclosure of potential conflicts of interest is found at the end of this article.