title: A functional interplay between ZNF217 and estrogen receptor alpha exists in luminal breast cancers.
abstract: We aimed at highlighting the role of ZNF217, a Krüppel-like finger protein, in Estrogen Receptor-α (ERα)-positive (ER+) and luminal breast cancers. Here we report for the first time that ZNF217 and ERα proteins bind to each other in both breast cancer cells and breast tumour samples, via the ERα hinge domain and the ZNF217 C-terminal domain. ZNF217 enhances the recruitment of ERα to its estrogen response elements (ERE) and the ERα-dependent transcription of the GREB1 estrogen-regulated gene. The prognostic power of ZNF217 mRNA expression levels is most discriminatory in breast cancers classified with a "good prognosis", particularly the Luminal-A subclass. A new immunohistochemistry ZNF217 index, based on nuclear and cytoplasmic ZNF217 staining, also allowed the identification of intermediate/poor relapse-free survivors in the Luminal-A subgroup. ZNF217 confers tamoxifen resistance in ER+ breast cancer cells and is a predictor of relapse under endocrine therapy in patients with ER+ breast cancer. ZNF217 thus allows the re-stratification of patients with ER+ breast cancers considered as cancers with good prognosis where no other biomarkers are currently available and widely used. Here we propose a model in ER+ breast cancer where ZNF217-driven aggressiveness incorporates ZNF217 as a positive enhancer of ERα direct genomic activity and where ZNF217 possesses its highest discriminatory prognostic value.
authors: ISPB, Faculté de Pharmacie, Lyon, France; Université Lyon 1, Lyon, France; INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors: Nhan T
authors: NT
authors: Nguyen
authors: ISPB, Faculté de Pharmacie, Lyon, France; Université Lyon 1, Lyon, France; INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors: Julie A
authors: JA
authors: Vendrell
authors: Université Lyon 1, Lyon, France; INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors: Coralie
authors: C
authors: Poulard
authors: MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary; 2nd Dept. of Pediatrics, Semmelweis University, Budapest, Hungary; MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.
authors: Balázs
authors: B
authors: Győrffy
authors: Centre Léon Bérard, Lyon, France.
authors: Sophie
authors: S
authors: Goddard-Léon
authors: Service de Génétique, Institut Curie, Paris, France.
authors: Ivan
authors: I
authors: Bièche
authors: Université Lyon 1, Lyon, France; INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors: Laura
authors: L
authors: Corbo
authors: Université Lyon 1, Lyon, France; INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors: Muriel
authors: M
authors: Le Romancer
authors: Centre Léon Bérard, Lyon, France.
authors: Thomas
authors: T
authors: Bachelot
authors: INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France; Centre Léon Bérard, Lyon, France.
authors: Isabelle
authors: I
authors: Treilleux
authors: ISPB, Faculté de Pharmacie, Lyon, France; Université Lyon 1, Lyon, France; INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France. Electronic address: pascale.cohen@univ-lyon1.fr.
authors: Pascale A
authors: PA
authors: Cohen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D015534:Trans-Activators; C113698:ZNF217 protein, human
keywords: Biomarker; Breast cancer; Endocrine therapy resistance; Estrogen Receptor-α; Estrogen signalling; ZNF217