Published in:
Open Access
01-12-2009 | Research article
The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice
Authors:
Paul Jedlicka, Xiaomei Sui, Arthur Gutierrez-Hartmann
Published in:
BMC Cancer
|
Issue 1/2009
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Abstract
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 ApcMin 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 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.
Conclusion
Our findings provide in vivo evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.