Elevated level of lysine 9-acetylated histone H3 at the MDR1 promoter in multidrug-resistant cells
| العنوان: | Elevated level of lysine 9-acetylated histone H3 at the MDR1 promoter in multidrug-resistant cells |
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| المؤلفون: | Eva Balint, Monika Toth, Imre Boros |
| المصدر: | Cancer Sci Europe PubMed Central |
| بيانات النشر: | Wiley, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cancer Research, ATP Binding Cassette Transporter, Subfamily B, Breast Neoplasms, Biology, SAP30, physiological processes, Histones, Cell Line, Tumor, Histone methylation, Histone H2A, polycyclic compounds, Humans, p300-CBP Transcription Factors, ATP Binding Cassette Transporter, Subfamily B, Member 1, Promoter Regions, Genetic, neoplasms, Histone Acetyltransferases, Lysine, EZH2, Acetylation, Original Articles, General Medicine, Molecular biology, HDAC4, Drug Resistance, Multiple, Gene Expression Regulation, Neoplastic, Histone Deacetylase Inhibitors, Histone, Oncology, Doxorubicin, Drug Resistance, Neoplasm, Histone methyltransferase, biology.protein, RNA Interference |
| الوصف: | 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. (Cancer Sci 2012; 103: 659–669) |
| تدمد: | 1347-9032 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b04683869971c38aaf61106bb7f60da4Test https://doi.org/10.1111/j.1349-7006.2012.02215.xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b04683869971c38aaf61106bb7f60da4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13479032 |
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