Title

The role of histone deacetylases in colon cancer epigenetics

Date of Completion

January 2009

Keywords

Biology, Genetics

Degree

Ph.D.

Abstract

Since the discovery of its structure in 1953, the DNA molecule has held the center-stage for research into cell fate determination and disease progression. More recently, however, the scope of this view has expanded to include epigenetic modifications—heritable changes that occur through mechanisms independent of the sequence itself. Epigenetic modifications are a critical mechanism in the differentiation of normal cells and also play a role in various diseases including cancer. Awareness of the epigenetic modifications that occur in cancer has helped to identify new targets for therapeutic intervention. Histone deacetylase enzymes, which affect the packaging of DNA, have recently been identified as one such target. Found to be over-expressed in many cancers, including colon cancer, this class of proteins represents an attractive target for treatment. In fact, several inhibitors of histone deacetylases have been identified that work to cause cell cycle arrest and differentiation in certain cancers. Most of these inhibitors, however, are not specific to any one HDAC enzyme, which suggests the possibility of confounding side effects. This work explores the individual class I HDAC enzymes and their roles in colon cancer cells' gene expression, with the hopes of assisting in the development of new targets for cancer chemoprevention and treatment. ^