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Journal of Mammary Gland Biology and Neoplasia

Published in:

Open Access 01-03-2010

Breast Cancer Epigenetics: From DNA Methylation to microRNAs

Authors: Jürgen Veeck, Manel Esteller

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 1/2010

Abstract

Both appropriate DNA methylation and histone modifications play a crucial role in the maintenance of normal cell function and cellular identity. In cancerous cells these “epigenetic belts” become massively perturbed, leading to significant changes in expression profiles which confer advantage to the development of a malignant phenotype. DNA (cytosine-5)-methyltransferase 1 (Dnmt1), Dnmt3a and Dnmt3b are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells. Intriguingly, DNMTs were found to be overexpressed in cancerous cells, which is believed to partly explain the hypermethylation phenomenon commonly observed in tumors. However, several lines of evidence indicate that further layers of gene regulation are critical coordinators of DNMT expression, catalytic activity and target specificity. Splice variants of DNMT transcripts have been detected which seem to modulate methyltransferase activity. Also, the DNMT mRNA 3′UTR as well as the coding sequence harbors multiple binding sites for trans-acting factors guiding post-transcriptional regulation and transcript stabilization. Moreover, microRNAs targeting DNMT transcripts have recently been discovered in normal cells, yet expression of these microRNAs was found to be diminished in breast cancer tissues. In this review we summarize the current knowledge on mechanisms which potentially lead to the establishment of a DNA hypermethylome in cancer cells.

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Title: Breast Cancer Epigenetics: From DNA Methylation to microRNAs
Authors: Jürgen Veeck
Manel Esteller
Publication date: 01-03-2010
Publisher: Springer US
Published in: Journal of Mammary Gland Biology and Neoplasia / Issue 1/2010
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI: https://doi.org/10.1007/s10911-010-9165-1

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Other articles of this Issue 1/2010

Gene Expression in the Third Dimension: The ECM-nucleus Connection

Epigenetic Modifications in 3D: Nuclear Organization of the Differentiating Mammary Epithelial Cell

Epigenetic Regulation of Milk Production in Dairy Cows

Tissue Polarity-Dependent Control of Mammary Epithelial Homeostasis and Cancer Development: an Epigenetic Perspective

The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation

Epigenetic Regulation in Estrogen Receptor Positive Breast Cancer—Role in Treatment Response

Keynote webinar | Spotlight on antibody–drug conjugates in cancer