Breast cancer epigenetics: from DNA methylation to microRNAs

J Mammary Gland Biol Neoplasia. 2010 Mar;15(1):5-17. doi: 10.1007/s10911-010-9165-1. Epub 2010 Jan 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • DNA Methylation / physiology*
  • DNA Modification Methylases / biosynthesis
  • DNA Modification Methylases / metabolism
  • Epigenesis, Genetic / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histones / metabolism
  • Humans
  • Isoenzymes / biosynthesis
  • Isoenzymes / metabolism
  • MicroRNAs / physiology*


  • Histones
  • Isoenzymes
  • MicroRNAs
  • DNA Modification Methylases