Search results for "EZH2"
showing 5 items of 15 documents
3-Deazaneplanocin A (DZNep), an Inhibitor of the Histone Methyltransferase EZH2, Induces Apoptosis and Reduces Cell Migration in Chondrosarcoma Cells
2014
Objective Growing evidences indicate that the histone methyltransferase EZH2 (enhancer of zeste homolog 2) may be an appropriate therapeutic target in some tumors. Indeed, a high expression of EZH2 is correlated with poor prognosis and metastasis in many cancers. In addition, 3-Deazaneplanocin A (DZNep), an S-adenosyl-L homocysteine hydrolase inhibitor which induces EZH2 protein depletion, leads to cell death in several cancers and tumors. The aim of this study was to determine whether an epigenetic therapy targeting EZH2 with DZNep may be also efficient to treat chondrosarcomas. Methods EZH2 expression was determined by immunohistochemistry and western-blot. Chondrosarcoma cell line CH2879…
PBDEs affect inflammatory and oncosuppressive mechanisms via the EZH2 methyltransferase in airway epithelial cells
2021
Abstract Aims We aimed to investigate the effect of PBDEs (47, 99, 209) on cellular events involved in epigenetic modification, inflammation, and epithelial mesenchymal transition (EMT). Materials and methods We studied: 1) ERK1/2 phosphorylation; 2) Enhancer of Zester Homolog 2 (EZH2); 3) Histone H3 tri-methylated in lysine 27 (H3K27me3); 4) K-RAS; 5) silencing disabled homolog 2-interacting protein gene (DAB2IP), 6) let-7a; 7) Muc5AC/Muc5B, and 8) IL-8 in a 3D in vitro model of epithelium obtained with primary Normal Human Bronchial Epithelial cells (pNHBEs) or A549 cell line, chronically exposed to PBDEs (47, 99, 209). Key findings PBDEs (10 nM, 100 nM and 1 μM) increased ERK1/2 phosphor…
Functional antagonism between histone H3K4 demethylases in vivo
2011
Dynamic regulation of histone modifications is critical during development, and aberrant activity of chromatin-modifying enzymes has been associated with diseases such as cancer. Histone demethylases have been shown to play a key role in eukaryotic gene transcription; however, little is known about how their activities are coordinated in vivo to regulate specific biological processes. In Drosophila, two enzymes, dLsd1 (Drosophila ortholog of lysine-specific demethylase 1) and Lid (little imaginal discs), demethylate histone H3 at Lys 4 (H3K4), a residue whose methylation is associated with actively transcribed genes. Our studies show that compound mutation of Lid and dLsd1 results in increa…
Involvement of EZH2-MYC loop and SALL4 in Epithelial-Mesenchymal Transition (EMT) and trastuzumab resistance process in HER2+ breast cancer
2021
Breast cancer (BC) is the most common type of cancer in females worldwide. It is also the second leading cause of death in women. BC is covered with heterogeneity properties, that leads to poor prognosis and therapeutic resistance. It has always been essential to unveil the different molecular mechanisms involved in BC cancer progression, finding a suitable treatment for the patients. This thesis focuses on unwrapping the various molecular mechanisms involved in HER2+ BC subtypes, as this denotes an aggressive phenotype among other subtypes of BC. Downregulation of miR-33b has been documented in many types of cancers and involves proliferation, migration, and epithelial-mesenchymal transiti…
EZH2 mutations are frequent and represent an early event in follicular lymphoma
2013
Gain of function mutations in the H3K27 methyltransferase EZH2 represent a promising therapeutic target in germinal center lymphomas. In this study, we assessed the frequency and distribution of EZH2 mutations in a large cohort of patients with follicular lymphoma (FL) (n = 366) and performed a longitudinal analysis of mutation during the disease progression from FL to transformed FL (tFL) (n = 33). Mutations were detected at 3 recurrent mutation hot spots (Y646, A682, and A692) in 27% of FL cases with variant allele frequencies (VAF) ranging from 2% to 61%. By comparing VAF of EZH2 with other mutation targets (CREBBP, MLL2, TNFRSF14, and MEF2B), we were able to distinguish patients harbori…