The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice
1 Department of Pathology, University of Colorado Denver, Aurora CO, USA
2 Department of Medicine, University of Colorado Denver, Aurora CO, USA
3 Department of Biochemistry, University of Colorado Denver, Aurora CO, USA
4 Department of Molecular Genetics, University of Colorado Denver, Aurora CO, USA
BMC Cancer 2009, 9:197 doi:10.1186/1471-2407-9-197Published: 22 June 2009
Ets transcription factors have been widely implicated in the control of tumorigenesis, with most studies suggesting tumor-promoting roles. However, few studies have examined Ets tumorigenesis-modifying functions in vivo using model genetic systems.
Using mice expressing a previously characterized Ets dominant repressor transgene in the intestinal epithelium (Villin-En/Erm), we examined the consequences of blocking endogenous Ets-mediated transcriptional activation on tumorigenesis in the ApcMin model of intestinal carcinoma.
En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in ApcMin animals. Moreover, when examined histologically, tumors from En/Erm-expressing animals show a trend toward greater stromal invasiveness. Detailed analysis of crypt-villus homeostasis in these En/Erm transgenic animals suggests increased epithelial turnover as one possible mechanism for the enhanced tumorigenesis.
Our findings provide in vivo evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.