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  • Original Paper
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EN2 is a candidate oncogene in human breast cancer

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.

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Acknowledgements

We thank Dr Alexandra Joyner (NYU, NYC) for En-1 and En-2 cDNAs and αEnhb-1 antisera; Dr Morag Park (McGill University, Montréal) for the BT-474, MDA-MB-231, SK-BR-3, MDA-MB-468, MDA-MB-435S, MCF 10A, MCF-12A, MDA-MB-436 and BT-20 cell lines; Dr Morag Park and Dr Michel Trudel (Montréal General Hospital, Montréal) for primary human breast tumor and normal adjacent tissue samples; Dr Shiu (University of Manitoba, Winnipeg) for the MCF7 and HBL 100 cell lines; Dr Paul Jolicoeur (IRCM) for the HC11 cell line; Dr Anthony Brown (Cornell University, NYC) for the C57MG cell line; Dr Robert Oshima (Burnham Institute, La Jolla) for human Keratin 18 cDNA; Christian Charbonneau for assistance in photography; and Annie Vallée and Martin Demers for histological sectioning services. This work was supported by funds from the NCIC (15064) to GS, and the NCIC to SM. NM is a recipient of a CIHR research award, GS is a scholar of the Leukemia and Lymphoma Society of USA and SM is an Investigator of the CIHR.

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Correspondence to Sylvain Meloche or Guy Sauvageau.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Martin, N., Saba-El-Leil, M., Sadekova, S. et al. EN2 is a candidate oncogene in human breast cancer. Oncogene 24, 6890–6901 (2005). https://doi.org/10.1038/sj.onc.1208840

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