Gene expression profile of Dclk1+ cells in intestinal tumors

Abstract

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.

Keywords: Colorectal cancer; Microarray analysis; Tumor stem cells.