ZNF703 gene amplification at 8p12 specifies luminal B breast cancer

EMBO Mol Med. 2011 Mar;3(3):153-66. doi: 10.1002/emmm.201100121.

Fabrice Sircoulomb ¹, Nathalie Nicolas, Anthony Ferrari, Pascal Finetti, Ismahane Bekhouche, Estelle Rousselet, Aurélie Lonigro, José Adélaïde, Emilie Baudelet, Séverine Esteyriès, Julien Wicinski, Stéphane Audebert, Emmanuelle Charafe-Jauffret, Jocelyne Jacquemier, Marc Lopez, Jean-Paul Borg, Christos Sotiriou, Cornel Popovici, François Bertucci, Daniel Birnbaum, Max Chaffanet, Christophe Ginestier

Affiliations

Affiliation

1 Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France.

PMID: 21328542 DOI: 10.1002/emmm.201100121

Abstract

Luminal B breast cancers represent a fraction of oestrogen receptor (ER)-positive tumours associated with poor recurrence-free and disease-specific survival in all Adjuvant systemic treatment categories including hormone therapy alone. Identification of specific signalling pathways driving luminal B biology is paramount to improve treatment. We have studied 100 luminal breast tumours by combined analysis of genome copy number aberrations and gene expression. We show that amplification of the ZNF703 gene, located in chromosomal region 8p12, preferentially occurs in luminal B tumours. We explored the functional role of ZNF703 in luminal B tumours by overexpressing ZNF703 in the MCF7 luminal cell line. Using mass spectrometry, we identified ZNF703 as a co-factor of a nuclear complex comprising DCAF7, PHB2 and NCOR2. ZNF703 expression results in the activation of stem cell-related gene expression leading to an increase in Cancer Stem Cells. Moreover, we show that ZNF703 is implicated in the regulation of ER and E2F1 transcription factor. These findings point out the prominent role of ZNF703 in transcription modulation, stem cell regulation and luminal B oncogenesis.

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