ABSTRACT
BACKGROUND: ESR1 is expressed by 60-70% of breast tumours. it's a good prognosis factor and the target of hormone therapy. Optimization of ESR1 reactivation therapy is currently ongoing. Here we probe if the transcription factor CTCF plays a role in the differential expression of ESR1 in the breast cancer cell lines MCF-7 (ESR1+) and MDA-MB-231 (ESR1-). METHODS AND RESULTS: Knockdown of CTCF in MCF-7 resulted in decreased ESR1 gene expression. CTCF binds to the promoter of ESR1 in MCF-7 but not in MDA-MB-231 cells. CTCF ESR1 binding sites are unmethylated in MCF7 but methylated in MDA-MB-231 cells. CONCLUSION: ESR1 expression in MCF7 cells is dependent on CTCF expression. CTCF can bind to specific regions of the promotor of ESR1 gene in MCF-7 cells but not in MDA-MB-231 cells, this correlates with the methylation status of these regions and could be involved in the transcriptional regulation of ESR1.
Subject(s)
Breast Neoplasms , CCCTC-Binding Factor , DNA Methylation , Estrogen Receptor alpha , Humans , DNA , DNA Methylation/genetics , MCF-7 Cells , MDA-MB-231 Cells , Breast Neoplasms/genetics , Promoter Regions, Genetic , CCCTC-Binding Factor/genetics , Estrogen Receptor alpha/geneticsABSTRACT
The aim of this study was to compare the kinetics of the in vivo action of equimolar doses of methyl gallate (MG) and epigallocatechin gallate (EGCG) on their capacity to induce DNA damage and to protect against DNA damage induced by 60 Co gamma rays. DNA-damaged cells were determined by single-cell gel electrophoresis (comets) in murine peripheral blood leukocytes. The maximum radioprotective effects of MG and EGCG (approximately 70%) occurred at 15 min after administration when their effect was determined 2 min following irradiation. MG and EGCG have similar radioprotective indexes, which due to their fast response indicate that they are involved in free radical scavenging. Due to the similar radioprotective activities of MG and EGCG, the in vivo radioprotective effects of these agents do not seem to be dependent on the number of hydroxyl groups present in their structures but instead on the presence of the galloyl radical. EGCG induces an early, significant, and persistent increase in the number of DNA-damaged cells and a later and more important increase in the number of damaged cells, suggesting that it has two mechanisms by which it can induce DNA damage. MG at the same molar dose as EGCG caused a significant and persistent increase in DNA damaged cells but to a much lesser extent to that induce by EGCG, suggesting that the galloyl radical is not involved in the mechanism of DNA breaks induction.
