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MCF-7和MDA-MB-231乳腺癌细胞ESR1启动子a之间的DNA甲基化差异及CTCF结合情况。

Differential DNA methylation and CTCF binding between the ESR1 promoter a of MCF-7 and MDA-MB-231 breast cancer cells.

作者信息

Montes-de-Oca-Fuentes Edén Víctor, Jácome-López Karina, Zarco-Mendoza Anaís, Guerrero Georgina, Ventura-Gallegos José Luis, Juárez-Méndez Sergio, Cabrera-Quintero Alberto Jose, Recillas-Targa Félix, Zentella-Dehesa Alejandro

机构信息

Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, 04510, México.

Programa de Investigación en Cáncer de Mama, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico.

出版信息

Mol Biol Rep. 2024 Jan 18;51(1):148. doi: 10.1007/s11033-023-09171-0.

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.

摘要

背景

60%-70%的乳腺肿瘤表达雌激素受体1(ESR1)。它是一个良好的预后因素,也是激素治疗的靶点。目前正在进行ESR1重新激活疗法的优化。在此,我们探究转录因子CCCTC结合因子(CTCF)是否在乳腺癌细胞系MCF-7(ESR1阳性)和MDA-MB-231(ESR1阴性)中ESR1的差异表达中发挥作用。

方法与结果

在MCF-7细胞中敲低CTCF导致ESR1基因表达降低。CTCF在MCF-7细胞中与ESR1的启动子结合,但在MDA-MB-231细胞中不结合。CTCF与ESR1的结合位点在MCF7细胞中未甲基化,但在MDA-MB-231细胞中甲基化。

结论

MCF7细胞中ESR1的表达依赖于CTCF的表达。CTCF可在MCF-7细胞中与ESR1基因启动子的特定区域结合,但在MDA-MB-231细胞中不结合,这与这些区域的甲基化状态相关,可能参与ESR1的转录调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b50/10796618/d2e5229eab4f/11033_2023_9171_Fig1_HTML.jpg

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