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表观遗传学、雌激素受体-α表达、HER2/ERBB2与三阴性乳腺癌细胞对激素治疗敏感性之间的相互作用

Interplay between Epigenetics, Expression of Estrogen Receptor- α, HER2/ERBB2 and Sensitivity of Triple Negative Breast Cancer Cells to Hormonal Therapy.

作者信息

Ramadan Wafaa S, Vazhappilly Cijo George, Saleh Ekram M, Menon Varsha, AlAzawi Aya M, El-Serafi Ahmed T, Mansour Wael, El-Awady Raafat

机构信息

Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE.

College of Medicine, University of Sharjah, Sharjah 27272, UAE.

出版信息

Cancers (Basel). 2018 Dec 21;11(1):13. doi: 10.3390/cancers11010013.

DOI:10.3390/cancers11010013
PMID:30583472
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6356506/
Abstract

Triple negative breast cancer (TNBC) cells are resistant to hormonal/targeted therapies. This study aims to investigate epigenetic differences between TNBC and other types of breast cancer and the effect of epigenetic modulation on the response of TNBC cells to hormonal therapy. Thus, we investigated (i) the expression of different epigenetic markers, (ii) the effect of epigenetic modifying agents on the expression of ERα and HER2/ERBB2 and (iii) the effect on the response to tamoxifen in four breast cancer cell lines with different hormonal receptor status. Our results revealed a differential expression patterns of epigenetic markers in the four breast cancer cells. In TNBC cells, histone deacetylases (HDAC) 1 and 2 were less expressed, whereas HDACs 4 and 6 were overexpressed. Interestingly, treatment with epigenetic modifiers resulted in (i) a pronounced increase in the expression of ERα and HER2/ERBB2 along with (ii) an increase in the sensitivity of TNBC cells to tamoxifen. Collectively, this study indicates a different epigenetic background for TNBC cells, which represses the expression of ERα and HER2/ERBB2. Furthermore, we provide here the rationale for the use of epigenetic modifiers to enhance the response of TNBC to hormonal therapy through upregulation of ERα.

摘要

三阴性乳腺癌（TNBC）细胞对激素/靶向治疗具有抗性。本研究旨在调查TNBC与其他类型乳腺癌之间的表观遗传差异，以及表观遗传调控对TNBC细胞对激素治疗反应的影响。因此，我们研究了：（i）不同表观遗传标志物的表达；（ii）表观遗传修饰剂对ERα和HER2/ERBB2表达的影响；以及（iii）对四种具有不同激素受体状态的乳腺癌细胞系中他莫昔芬反应的影响。我们的结果揭示了四种乳腺癌细胞中表观遗传标志物的差异表达模式。在TNBC细胞中，组蛋白去乙酰化酶（HDAC）1和2表达较少，而HDAC4和6过表达。有趣的是，用表观遗传修饰剂处理导致：（i）ERα和HER2/ERBB2的表达显著增加，以及（ii）TNBC细胞对他莫昔芬的敏感性增加。总体而言，本研究表明TNBC细胞具有不同的表观遗传背景，其抑制了ERα和HER2/ERBB2的表达。此外，我们在此提供了使用表观遗传修饰剂通过上调ERα来增强TNBC对激素治疗反应的理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/8aaa4a9ae364/cancers-11-00013-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/66f1d30d82fb/cancers-11-00013-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/d35631a4169a/cancers-11-00013-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/d481dac5cc73/cancers-11-00013-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/a37d6b9a9398/cancers-11-00013-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/3f57db8a7104/cancers-11-00013-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/9e8c0d3d04e2/cancers-11-00013-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/8aaa4a9ae364/cancers-11-00013-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/66f1d30d82fb/cancers-11-00013-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/d35631a4169a/cancers-11-00013-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/d481dac5cc73/cancers-11-00013-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/a37d6b9a9398/cancers-11-00013-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/3f57db8a7104/cancers-11-00013-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/9e8c0d3d04e2/cancers-11-00013-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ef/6356506/8aaa4a9ae364/cancers-11-00013-g007.jpg

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