Epigenetics refers to the inheritance of information about chemical modifications without the DNA sequence changing (Jaenisch and Bird 2003). In contrast to genetics, epigenetics deals with modifications of DNA and DNA-binding proteins and histones, which lead to a change in the chromatin structure, without changing the nucleotide sequence of the DNA
In cancer, the regulation of DNA methylation stops working and the distribution of 5-mC in the genome changes. Despite hypermethylation in some promoter regions, which are normally unmethylated, and the presence of increased DNMT1 activity in cancer, all types of cancer studied to date are characterized by global hypomethylation. In cancer, two opposing changes in DNAMethylation can be observed: regional hypermethylation of tumor suppressor genes and global, genome-wide hypomethylation.
Inhibition of Metastasis
In fact, hypermethylation plays an extremely important role in cancer and cancer development. Nevertheless, hypomethylation acts as a mechanism that could lead to the activation of genes responsible for motility, migration, and invasion (Shahrzad, Bertrand et al., 2007). MCF7 is not a metastatic cell line, but MDA-MB-231 is characterized by high invasiveness.
The protease urokinase-type plasminogen activator, which is responsible for invasion, is normally not expressed in MCF7 and hypermethylated. After treatment with 5 aza-CDR, it is demethylated and expressed, resulting in the transformation of the MCF7 line into the invasive cell line (Guo, Pakneshan et al., 2002).
DNA methylation is a covalent modification that can occur in cytosine residues within CpG-rich regions of DNA and is catalyzed by DNA methyltransferases (Klose and Bird 2006). Such attachment of methyl groups may prevent binding of the basal transcription factors. Thus, methylation can lead to certain genes can not be expressed
This project is a starting point for further investigation and provide us with new insights into the pathogenesis of mammakarzinoms and new hope for the development of novel targeted molecular therapies.