The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in Apc(Min )mice

BACKGROUND: 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. METHODS: 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 Apc(Min )model of intestinal carcinoma. RESULTS: En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in Apc(Min )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. CONCLUSION: Our findings provide in vivo evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.