Abstract
The progression through the multiple steps of breast cancer from epithelial hypertrophy to highly invasive breast carcinoma involves multiple coordinated changes in gene expression programming. Such coordinated changes in gene expression are bound to be controlled by global mechanisms of gene expression programming. The genome is programmed by the epigenome, which consists of chromatin structure, a pattern of modification of DNA by DNA methylation and a profile of expression of noncoding RNAs such as microRNA. This chapter will focus on DNA methylation. Three kinds of aberrations in the DNA methylation machinery were observed in breast cancer: induction of DNA methyltransferase activity, hypermethylation of tumor suppressing genes, and hypomethylation of other genes. The main focus of attention has been hypermethylation of tumor suppressor genes and demethylation inducing therapies. Recent data suggest that hypomethylation of prometastatic genes might play an important role in cancer progression and metastasis. The implications of coexistence of hypermethylation and hypomethylation in breast for epigenetic therapy will be discussed.
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