Breast Cancer

Biography

Biography: Pascale Cohen

Abstract

ZnFX (Zinc Finger Protein) is an oncogenic transcription factor that induces Epithelial Mesenchymal Transition, increased invasive properties and resistance to chemotherapy. ZnFX is known to repress or activate genes involved in survival pathway and cell proliferation. We aimed to investigate the effect of ZnFX’s C-terminus on cell proliferation and genomic DNA binding. ZnFX was knocked-out in MDA-MB231 (breast cancer cells) cells to yield Cl73 cells (Cl73-ΔZnFX). The Cl73-ΔZnFX cells were stably transfected with ZnFX WT, ZnFX Δ1014-1048 or ZnFX Δ747-1048 isoforms. We found that the knocking-out ZnFX reduces proliferation of MDA-MB231 cells. Re-expression of ZnFX WT or ZnFX Δ1014-1048 enhances proliferation of Cl73-ΔZnFX cells, while ZnFX Δ747-1048 did not have an impact on Cl73 proliferation. Thus, we deduced that the absence of ZnFX or the 301 amino-acid truncation in its C-terminus decreased proliferation of MDA-MB231. This suggests that the ZnFX’s c-terminus may positively regulate cell proliferation. To better determine how truncation of ZnFX affects its genomic binding dynamics, we performed Single Particle Tracking Microscopy. We found that the ZnFX Δ747-1048 isoform resides on chromatin for significantly shorter time periods relative to ZnFX WT and ZnFX Δ1014-1048 isoform. We thus deduced that the 301 amino-acid (aa) sequence (possessing the transcriptional repressor domain) lacking in the Δ747-1048 isoform is crucial for genomic binding. These preliminary data suggest that deregulated ZnFX‘s DNA-binding behavior, driven by its 301 aa C-terminus sequence, is paired with defect in stimulating cell proliferation