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

Stem Cells. 2008 Mar;26(3):630-7. doi: 10.1634/stemcells.2007-0621. Epub 2007 Nov 29.

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 beta-catenin in normal-appearing intestine. However, beta-catenin was nuclear in DCAMKL-1-positive cells in adenomas. Thus, nuclear translocation of beta-catenin distinguishes normal and adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing novel chemotherapeutic agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenomatous Polyposis Coli / metabolism*
  • Animals
  • Biomarkers, Tumor / metabolism*
  • Gastrointestinal Tract / cytology*
  • Gastrointestinal Tract / radiation effects
  • Intestinal Mucosa / metabolism
  • Intestinal Neoplasms / metabolism*
  • Intestines / cytology
  • Intestines / pathology
  • Intestines / radiation effects
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Protein Transport / radiation effects
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA-Binding Proteins / metabolism
  • Radiation, Ionizing
  • Regeneration / radiation effects
  • Stem Cells / cytology*
  • Stem Cells / radiation effects
  • beta Catenin / metabolism

Substances

  • Biomarkers, Tumor
  • Msi1h protein, mouse
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • beta Catenin
  • Dcamkl1 protein, mouse
  • Protein-Serine-Threonine Kinases