Up-regulation of<i>HOXB</i>cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells

Yang, Seoyeon; Lee, Ji Yeon; Hur, Ho; Oh, Ji Hoon; Kim, Myoung Hee

doi:10.5483/bmbrep.2018.51.9.020

Cited by 20 publications

(12 citation statements)

References 31 publications

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“…Moreover, the small clinical study on 22 patients has suggested benefit of this practice even in the determination of response to a chemotherapy 31 . Further, epigenetics is now understood to play big role in determination of drug sensitivity in breast cancer 32 , even in the delicate balance between resistance and sensitivity to tamoxifen 33–36 . This not only suggests that our work is timely, but also calls for further studies to improve our understanding of the underlying mechanisms, which can lead to much improved targeted therapies for the treatment of estrogen receptor-expressing breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Induced Tamoxifen Resistance is Mediated by Increased Methylation of E-Cadherin in Estrogen Receptor-Expressing Breast Cancer Cells

Wang

Gun

Hong

2019

Sci Rep

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Estrogen receptor-positive breast cancers are treated with tamoxifen, a drug that competitively inhibits the binding of estrogen to its receptor. Resistance to tamoxifen is a major hurdle in effective management of target breast cancer patient population. A number of dynamic changes within the tumor microenvironment, including the phenomenon of epithelial to mesenchymal transition (EMT), determine the response to endocrine therapy. EMT is marked by silencing or suppression of epithelial marker, E-Cadherin and we found significantly down-regulated E-Cadherin, among other epithelial markers, and a significantly up-regulated mesenchymal marker, Twist, among other mesenchymal markers, in a model system that comprised of tamoxifen sensitive MCF-7 cells and their tamoxifen-resistant counterparts, MCF-7-TAM, developed by chronic and escalating exposure of parental cells to tamoxifen. Further, E-cadherin, but not Twist, was differentially expressed in MCF-7-TAM cells because of differential methylation. Treatment with demethylating agent 5-azacytidine increased the expression of E-cadherin thus verifying a role of methylation in its silencing and, moreover, 5-azacytidine treatment also re-sensitized MCF-7-TAM cells to tamoxifen, as evaluated by assays for viability, apoptosis and migration potential. The 5-azacytidine effects were similar to effects of E-cadherin overexpression in MCF-7-TAM cells. This work describes novel mechanism of E-cadherin downregulation in tamoxifen resistant breast cancer cells. Further studies are needed to exploit this information for betterment of breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Induced Tamoxifen Resistance is Mediated by Increased Methylation of E-Cadherin in Estrogen Receptor-Expressing Breast Cancer Cells

Wang

Gun

Hong

2019

Sci Rep

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“…HoxB genes are transcription factors involved in development [ 30 ] and whose activation is regulated by chromatin domain boundaries [ 31 , 32 ]. Recently, Hox genes have been shown to transcriptionally activate EGFR in drosophila [ 33 ] and breast cancer cells [ 34 ], although their role in EGFR-driven lung tumors is largely uncharacterized. Among other significant domains, we found several cancer-associated genes.…”

Section: Resultsmentioning

confidence: 99%

Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers

et al. 2021

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Background Spatial interactions and insulation of chromatin regions are associated with transcriptional regulation. Domains of frequent chromatin contacts are proposed as functional units, favoring and delimiting gene regulatory interactions. However, contrasting evidence supports the association between chromatin domains and transcription. Result Here, we assess gene co-regulation in chromatin domains across multiple human cancers, which exhibit great transcriptional heterogeneity. Across all datasets, gene co-regulation is observed only within a small yet significant number of chromatin domains. We design an algorithmic approach to identify differentially active domains (DADo) between two conditions and show that these provide complementary information to differentially expressed genes. Domains comprising co-regulated genes are enriched in the less active B sub-compartments and for genes with similar function. Notably, differential activation of chromatin domains is not associated with major changes of domain boundaries, but rather with changes of sub-compartments and intra-domain contacts. Conclusion Overall, gene co-regulation is observed only in a minority of chromatin domains, whose systematic identification will help unravel the relationship between chromatin structure and transcription.

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“…Our findings discovered the interaction of HOXA5 with HOXB6 and HOXB7 . The downregulation of HOXA5 increased the expression of HOXB6 and HOXB7, which were associated with poor clinical outcomes in cancer patients [ 83 , 84 , 85 ]. On the other hand, the hypermethylation of ADHFE1 further reduced the expression of neighbouring proteins, ADH6 , ADH7, as well as ADH1A, in which the genes were associated with the patient’s prognosis and cancer pathogenesis [ 86 , 87 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

Baharudin

Ishak

Yusof³

et al. 2022

Diagnostics

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The aims were to profile the DNA methylation in colorectal cancer (CRC) and to explore cancer-specific methylation biomarkers. Fifty-four pairs of CRCs and the adjacent normal tissues were subjected to Infinium Human Methylation 450K assay and analysed using ChAMP R package. A total of 26,093 differentially methylated probes were identified, which represent 6156 genes; 650 probes were hypermethylated, and 25,443 were hypomethylated. Hypermethylated sites were common in CpG islands, while hypomethylated sites were in open sea. Most of the hypermethylated genes were associated with pathways in cancer, while the hypomethylated genes were involved in the PI3K-AKT signalling pathway. Among the identified differentially methylated probes, we found evidence of four potential probes in CRCs versus adjacent normal; HOXA2 cg06786372, OPLAH cg17301223, cg15638338, and TRIM31 cg02583465 that could serve as a new biomarker in CRC since these probes were aberrantly methylated in CRC as well as involved in the progression of CRC. Furthermore, we revealed the potential of promoter methylation ADHFE1 cg18065361 in differentiating the CRC from normal colonic tissue from the integrated analysis. In conclusion, aberrant DNA methylation is significantly involved in CRC pathogenesis and is associated with gene silencing. This study reports several potential important methylated genes in CRC and, therefore, merit further validation as novel candidate biomarker genes in CRC.

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Up-regulation ofHOXBcluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells

Cited by 20 publications

References 31 publications

Induced Tamoxifen Resistance is Mediated by Increased Methylation of E-Cadherin in Estrogen Receptor-Expressing Breast Cancer Cells

Induced Tamoxifen Resistance is Mediated by Increased Methylation of E-Cadherin in Estrogen Receptor-Expressing Breast Cancer Cells

Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

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