title: ZNF703 gene amplification at 8p12 specifies luminal B breast cancer.
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.
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Sircoulomb
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicolas
authors.forename: Anthony
authors.initials: A
authors.lastname: Ferrari
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Ismahane
authors.initials: I
authors.lastname: Bekhouche
authors.forename: Estelle
authors.initials: E
authors.lastname: Rousselet
authors.forename: Aurélie
authors.initials: A
authors.lastname: Lonigro
authors.forename: José
authors.initials: J
authors.lastname: Adélaïde
authors.forename: Emilie
authors.initials: E
authors.lastname: Baudelet
authors.forename: Séverine
authors.initials: S
authors.lastname: Esteyriès
authors.forename: Julien
authors.initials: J
authors.lastname: Wicinski
authors.forename: Stéphane
authors.initials: S
authors.lastname: Audebert
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Marc
authors.initials: M
authors.lastname: Lopez
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Cornel
authors.initials: C
authors.lastname: Popovici
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D013058:Mass Spectrometry; D000091402:Prohibitins; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011960:Receptors, Estrogen; C541016:ZNF703 protein, human