ArticleClinical epigenetics2015
Genome-wide DNA methylation analysis reveals estrogen-mediated epigenetic repression of metallothionein-1 gene cluster in breast cancer.
Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Palladium-catalysed synthesis of small-molecule epigenetic inhibitors as anticancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Steroid hormone-mediated epigenetic programming during puberty: uncovering links to depression.Epigenomics · 2025Review
- Identification of copper related biomarkers in breast cancer using machine learning.Discover oncology · 2025Article
- Cancer Drug Sensitivity Prediction Based on Deep Transfer Learning.International journal of molecular sciences · 2025Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women.Frontiers in oncology · 2023Article
- Functional regulations between genetic alteration-driven genes and drug target genes acting as prognostic biomarkers in breast cancer.Scientific reports · 2022Article
- 2-Hydroxyglutarate destabilizes chromatin regulatory landscape and lineage fidelity to promote cellular heterogeneity.Cell reports · 2022Article
- Metabolic and Epigenetic Regulation by Estrogen in Adipocytes.Frontiers in endocrinology · 2022Review
- MetallothioneinMolecules and cells · 2021Article
- Modeling and analysis of Hi-C data by HiSIF identifies characteristic promoter-distal loops.Genome medicine · 2020Article
- Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis.PLoS genetics · 2020Article
- ERα-related chromothripsis enhances concordant gene transcription on chromosome 17q11.1-q24.1 in luminal breast cancer.BMC medical genomics · 2020Article
- Metallothionein 1M (MT1M) inhibits lung adenocarcinoma cell viability, migration, and expression of cell mobility-related proteins through MDM2/p53/MT1M signaling.Translational cancer research · 2020Article
- Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray.Biomolecules · 2019Article
- Metallothionein Genes are Highly Expressed in Malignant Astrocytomas and Associated with Patient Survival.Scientific reports · 2019Article
- Early synergistic interactions between the HPV16‑E7 oncoprotein and 17β-oestradiol for repressing the expression of Granzyme B in a cervical cancer model.International journal of oncology · 2018Article
- Potential Mechanisms of Age Acceleration Caused by Estrogen Deprivation: Do Endocrine Therapies Carry the Same Risks?JNCI cancer spectrum · 2018Review
- Gestational oral low-dose estradiol-17β induces altered DNA methylation of CDKN2D and PSAT1 in embryos and adult offspring.Scientific reports · 2018Article
- Estradiol and the Development of the Cerebral Cortex: An Unexpected Role?Frontiers in neuroscience · 2018Review
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundRecent genome-wide analysis has shown that DNA methylation spans long stretches of chromosome regions consisting of clusters of contiguous CpG islands or gene families. Hypermethylation of various gene clusters has been reported in many types of cancer. In this study, we conducted methyl-binding domain capture (MBDCap) sequencing (MBD-seq) analysis on a breast cancer cohort consisting of 77 patients and 10 normal controls, as well as a panel of 38 breast cancer cell lines.
resultsBioinformatics analysis determined seven gene clusters with a significant difference in overall survival (OS) and further revealed a distinct feature that the conservation of a large gene cluster (approximately 70 kb) metallothionein-1 (MT1) among 45 species is much lower than the average of all RefSeq genes. Furthermore, we found that DNA methylation is an important epigenetic regulator contributing to gene repression of MT1 gene cluster in both ERα positive (ERα+) and ERα negative (ERα-) breast tumors. In silico analysis revealed much lower gene expression of this cluster in The Cancer Genome Atlas (TCGA) cohort for ERα + tumors. To further investigate the role of estrogen, we conducted 17β-estradiol (E2) and demethylating agent 5-aza-2'-deoxycytidine (DAC) treatment in various breast cancer cell types. Cell proliferation and invasion assays suggested MT1F and MT1M may play an anti-oncogenic role in breast cancer.
conclusionsOur data suggests that DNA methylation in large contiguous gene clusters can be potential prognostic markers of breast cancer. Further investigation of these clusters revealed that estrogen mediates epigenetic repression of MT1 cluster in ERα + breast cancer cell lines. In all, our studies identify thousands of breast tumor hypermethylated regions for the first time, in particular, discovering seven large contiguous hypermethylated gene clusters.
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