The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin 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 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.


CONCLUSIONS
Our findings provide in vivo evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.
Jedlicka
Paul
P
Department of Pathology, University of Colorado Denver, Aurora CO, USA. paul.jedlicka@ucdenver.edu
Sui
Xiaomei
X
Gutierrez-Hartmann
Arthur
A
D000818:Animals; D002277:Carcinoma / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D008957:Models, Genetic; D009361:Neoplasm Invasiveness; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D019076:Transgenes
D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors