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.