Chapter 4 - Epigenetics and animal models: applications in cancer control and treatment

Abstract

Epigenetic mechanism is involved in most of the diseases including cancer, cardiovascular diseases, diabetes, neurological disorders, and autoimmune diseases. In contrast to genetics which is based on changes in nucleotide sequences, epigenetics involves gene expression alterations in normal and disease states without changes in DNA sequence. Research conducted in last decade indicated that cancer is a genetic and epigenetic disease. Genetically engineered tumor-prone mouse models have proven to be powerful tools in understanding many aspects of carcinogenesis, including epigenetics. DNA methylation, histone modifications, noncoding RNA profiling, and chromatin condensation and relaxation (accessibility to chromatin) are major components of epigenetic regulatory machinery. DNA methylation in particular has been the subject of intense interest because of its recently recognized role in disease initiation, development, and progression, as well as in the development and normal function of organisms. Starting from cell line systems and simple model systems such as Arabidopsis thaliana, more complex model systems have led to further insights in the role of epigenetics in human diseases. This article focuses on cancer because, compared with other diseases, cancer epigenetics has been studied extensively—from diagnostics to prognosis to therapy and survival, and epigenetic inhibitors have been used successfully in treating specific cancers. Selected epigenetics animal models in brain, breast, liver, lung, blood, colon, and prostate cancers are described. Challenges in the field and potential solutions also are discussed.