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

Randal May, Terrence E. Riehl, Clayton Hunt, Sripathi M. Sureban, Shrikant Anant, Courtney W. Houchen

Research output: Contribution to journalArticle

218 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)630-637
Number of pages8
JournalSTEM CELLS
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

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

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