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.
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.
Department of Medicine, University of Oklahoma Health Sciences Center, 920 Stanton L. Young Boulevard, WP 1360, Oklahoma City, Oklahoma 73104, USA.
Randal
R
May
Terrence E
TE
Riehl
Clayton
C
Hunt
Sripathi M
SM
Sureban
Shrikant
S
Anant
Courtney W
CW
Houchen
D011125:Adenomatous Polyposis Coli / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000089742:Doublecortin-Like Kinases; D041981:Gastrointestinal Tract / Q000166:cytology* / Q000528:radiation effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000528:radiation effects; D016601:RNA-Binding Proteins / Q000378:metabolism; D011839:Radiation, Ionizing; D012038:Regeneration / Q000528:radiation effects; D013234:Stem Cells / Q000166:cytology* / Q000528:radiation effects; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; C104786:Msi1h protein, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D051176:beta Catenin; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases