Identification of a Novel Putative Gastrointestinal Stem Cell and Adenoma Stem Cell Marker: DCAMKL-1 Following Radiation Injury and in APC/Min Mice

¹ Department of Medicine, Oklahoma University Health Sciences Center, Oklahoma City, OK 73134
² Department of Internal Medicine, Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO 63110
³ Department of Radiation Oncology, Radiation and Cancer Biology Division, Washington University School of Medicine, Saint Louis, MO 63110
⁴ Department of Medicine, Department of Cell Biology, Oklahoma University Health Sciences Center, Oklahoma City, OK 73134

^* To whom correspondence should be addressed. E-mail: Courtney-houchen{at}ouhsc.edu.

	Abstract

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 utilized the putative stem cell marker doublecortin and CaM kinase-Like (DCAMKL)-1 to examine radiation-induced stem cell apoptosis and adenomatous polyposis coli (APC)/min (multiple intestinal neoplasia) mice to determine the effects of APC mutation on DCAMKL-1 expression. Immunoreactive DCAMKL-1 staining is demonstrated in the intestinal stem cell zone. Furthermore, we observed apoptosis of the cells negative for DCAMKL-1 at 6hr. 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 24hr after irradiation. Moreover, in APC/min mice, DCAMKL-1 expressing cells were negative for proliferating cell nuclear antigen (PCNA) and nuclear -catenin in normal appearing intestine. However, -catenin was nuclear in DCAMKL-1 positive cells in adenomas. Thus nuclear translocation of -catenin distinguishes normal and adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing novel chemotherapeutic agents.