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2013 Research Abstract

The Role of DNA Methylation in Tumor Maintenance

Investigator: Charlene Fares

Mentor: Peter Laird, PhD

Abstract:The role of epigenetics in cancer is a rapidly emerging and important field in cancer biology. Gene silencing of tumor suppressors by promoter methylation has been identified as an essential epigenetic mechanism in tumorigenesis. Many studies have demonstrated that DNA methylation plays a crucial role in tumor initiation, however the contribution of aberrant promoter methylation to tumor maintenance remains unknown. The goal of our project is to determine if DNA methylation is required for continued tumor maintenance. To do this, we have developed a novel mouse model of colorectal cancer in which DNA methylation can be inducibly inhibited from established intestinal tumors. Tight inhibition of DNA methylation is accomplished by transcriptionally repressing a major DNA methyltransferase gene, Dnmt1. The novelty in our method lies in its ability to repress DNA methylation after tumors have developed under physiological epigenetic influences. Preliminary results suggest potential tumor regression in the small intestine following suppression of DNA methylation. Tumor regression was explored further using various biochemical approaches to detect apoptosis and senescence which are two well-known mechanisms of tumor regression. Apoptosis and senescence were examined at several time points after inhibition of DNA methylation. Both apoptosis and senescence assays did not demonstrate a significant change upon inhibition of DNA methylation at the investigated time points. Research remains ongoing using a larger sample size at additional time points, advanced small animal imaging modalities and a cell line developed from intestinal polyps.

Last updated: 10/2/2014

Updated on September 2, 2014.