A functional interplay between ZNF217 and Estrogen Receptor alpha exists in luminal breast cancers

作者：Nguyen Nhan T; Vendrell Julie A; Poulard Coralie; Gyorffy Balazs; Goddard Leon Sophie; Bieche Ivan; Corbo Laura; Le Romancer Muriel; Bachelot Thomas; Treilleux Isabelle; Cohen Pascale A^*

来源：Molecular Oncology, 2014, 8(8): 1441-1457.

DOI：10.1016/j.molonc.2014.05.013

• ZNF217
• Estrogen Receptor-alpha
• Breast cancer
• Estrogen signalling
• Biomarker
• Endocrine therapy resistance

We aimed at highlighting the role of ZNF217, a Kruppel-like finger protein, in Estrogen Receptor-alpha (ER alpha)-positive (ER+) and luminal breast cancers. Here we report for the first time that ZNF217 and ER alpha proteins bind to each other in both breast cancer cells and breast tumour samples, via the ER alpha hinge domain and the ZNF217 C-terminal domain. ZNF217 enhances the recruitment of ER alpha to its estrogen response elements (ERE) and the ER alpha-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 %26quot;good prognosis%26quot;, 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 ER alpha direct genomic activity and where ZNF217 possesses its highest discriminatory prognostic value.

• 出版日期2014-12