ArticleCancer science2012
Elevated level of lysine 9-acetylated histone H3 at the MDR1 promoter in multidrug-resistant cells.
Article in Cancer science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 65 citations in OpenAlex.
- Interindividual epigenetic variation in ABCB1 promoter and its relationship with ABCB1 expression and function in healthy Chinese subjects.British journal of clinical pharmacology · 2015Trial
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Epigenetic plasticity in cancer drug resistance: mechanistic insights and strategies for therapeutic intervention.Acta pharmacologica Sinica · 2026Review
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- H3K14: A histone site closely related to diseases.Journal of Cancer · 2025Review
- A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance.Oncogene · 2024Review
- Histone acetylation: a key determinant of acquired cisplatin resistance in cancer.Clinical epigenetics · 2024Article
- Breast Cancer Chemoresistance: Insights into the Regulatory Role of lncRNA.International journal of molecular sciences · 2023Review
- β-Lapachone Exerts Anticancer Effects by Downregulating p53, Lys-Acetylated Proteins, TrkA, p38 MAPK, SOD1, Caspase-2, CD44 and NPM in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells.International journal of molecular sciences · 2023Article
- Semi-Synthetic Dihydrotestosterone Derivatives Modulate Inherent Multidrug Resistance and Sensitize Colon Cancer Cells to Chemotherapy.Pharmaceutics · 2023Article
- Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.Frontiers in pharmacology · 2023Review
- Activation ofCancers · 2022Article
- The Emerging Roles of Circular RNAs in the Chemoresistance of Gastrointestinal Cancer.Frontiers in cell and developmental biology · 2022Review
- Functionalized Mesoporous Silica Nanoparticles for Drug-Delivery to Multidrug-Resistant Cancer Cells.International journal of nanomedicine · 2022Article
- Histone Acetylation Domains Are Differentially Induced during Development of Heart Failure in Dahl Salt-Sensitive Rats.International journal of molecular sciences · 2021Article
- Carnosol Is a Novel Inhibitor of p300 Acetyltransferase in Breast Cancer.Frontiers in oncology · 2021Article
- Targeting Histone Modifications in Breast Cancer: A Precise Weapon on the Way.Frontiers in cell and developmental biology · 2021Review
- Epigenetic Regulation of Multidrug Resistance Protein 1 and Breast Cancer Resistance Protein Transporters by Histone Deacetylase Inhibition.Drug metabolism and disposition: the biological fate of chemicals · 2020Review
- ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance.International journal of molecular sciences · 2020Article
- Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells.Journal of nanobiotechnology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Failure of chemotherapy in breast cancer presents a major problem and is often due to elevated expression of ATP binding cassette (ABC)-type transporters, such as MDR1 protein. It has been shown that MDR1/ABCB1 gene expression is regulated at the chromatin level by DNA methylation and histone acetylation. However, the modified histone residues have not been identified and the role of various histone acetyl transferases (HATs) is not fully understood. By studying a breast carcinoma model cell line and its MDR1-overexpressing derivative, we show that the histone 3 lysine 9 (H3K9) acetylation level is elevated 100-fold in the promoter and first exon of the MDR1 gene in the drug-resistant cell line compared to the drug-sensitive cell line. The acetylation level of the other examined lysine residues (H3K4, H3K14, H4K8, and H4K12) is weakly or not at all elevated in the MDR1 locus, although their acetylation is generally increased genome-wide in the drug-resistant cell. Downregulation of the expression of HATs PCAF and GCN5 by RNAi effectively reduces the expression of MDR1. Unexpectedly, treatment with a p300-selective inhibitor (HAT inhibitor II) further increases MDR1 expression and drug efflux in the drug-resistant cells. Our data suggest that repeated exposure to chemotherapy may result in deregulated histone acetylation genome-wide and in the MDR1 promoter.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.