1. ¹Laboratory of Molecular Genetics of Hematopoietic Stem Cells, Institut de Recherche en Immunologie et Cancérologie, CP 6128, succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7
2. ²Laboratory of Signaling and Cell Growth, Institut de Recherche en Immunologie et Cancérologie, CP 6128, succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7
3. ³Department of Oncology, Mc Gill University, 3775 University, 205 Montreal, Québec, Canada H3A-2B4
4. ⁴Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada
5. ⁵Division of Hematology and Leukemia Cell Bank of Québec, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada

Correspondence: G Sauvageau and S Meloche, Laboratory of Molecular Genetics of Hematopoietic Stem Cells, Institut de Recherches en Immunologie et Cancérologie, CP 6128, succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7. E-mails: guy.sauvageau@umontreal.ca; sylvain.meloche@umontreal.ca

Received 24 March 2003; Revised 11 May 2005; Accepted 11 May 2005; Published online 20 June 2005.

Abstract

Only a few critical oncogenes have been identified in the more commonly occurring cases of sporadic breast cancer. We provide evidence that EN2 is ectopically expressed in a subset of human breast cancer and may have a causal role in mammary tumorigenesis. Nontumorigenic mammary cell lines engineered to ectopically express En-2 have a marked reduction in their cycling time, lose cell contact inhibition, become sensitive to 17-AAG treatment, fail to differentiate when exposed to lactogenic hormones and induce mammary tumors when transplanted into cleared mammary glands of syngeneic hosts. RNA interference studies suggest that EN2 expression is required for the maintenance of the transformed phenotype of a human breast tumor cell line.