Gene expression profile of Dclk1<sup>+</sup> cells in intestinal tumors.

Overview

BACKGROUND: Accumulating evidence has shown the existence of tumor stem cells with therapeutic potential. Previously, we reported that doublecortin like kinase 1 (Dclk1) marks tumor stem cells but not normal stem cells in the intestine of Apc^Min/+ mice, and that Dclk1- and Lgr5-double positive tumor cells are the tumor stem cells of intestinal tumors. AIM: To investigate molecules highly expressed in the Dclk1⁺ normal intestinal and Dclk1⁺ tumor cells in Apc^Min/+ mice. METHODS: We used microarray analyses to examine the gene expression profile of Dclk1⁺ cells in both mouse normal intestinal epithelium and Apc^Min/+ mouse intestinal tumors. We also performed immunofluorescence analyses. RESULTS: Genes related to microtubules and the actin cytoskeleton (e.g., Rac2), and members of the Src family kinases (i.e., Hck, Lyn, Csk, and Ptpn6) were highly expressed in both Dclk1⁺ normal intestinal and Dclk1⁺ tumor cells. Phosphorylated Hck and phosphorylated Lyn were expressed in Lgr5⁺ cells in the intestinal tumors of Lgr5^{EGFP-IRES-CreERT2/+}; Apc^Min/+ mice. CONCLUSION: We revealed factors that are highly expressed in Dclk1⁺ intestinal tumor cells, which may help to develop cancer stem cell-targeted therapy in future.

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver Journal