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STUDIES ON THE ALTERATION OF DNA METHYLATION IN CANCER
by
Si Ho Choi
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR PHARMACOLOGY AND TOXICOLOGY)
August 2008
Copyright 2008 Si Ho Choi
Object Description
| Title | Studies on the alteration of dna methylation in cancer |
| Author | Choi, Si Ho |
| Author email | sichoi@usc.edu; sichoi@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Pharmacology & Toxicology |
| School | School of Pharmacy |
| Date defended/completed | 2008-06-23 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-08-01 |
| Advisor (committee chair) | Cadenas, Enrique |
| Advisor (committee member) |
Yang, Allen S. Haworth, Ian S. |
| Abstract | "Epigenetics" can be defined as heritable changes in gene expression that are not due to changes in the DNA sequence (Holliday, 1987). Epigenetic can explain how different tissues that are genetically identical can have tissue specific phenotypes and functions (Fraga et al., 2005a; Futscher et al., 2002).; DNA methylation is a key repressive epigenetic mechanism of gene expression related to development, imprinting, X-chromosome inactivation (Beard et al., 1995; Li et al., 1993; Li et al., 1992; Venolia et al., 1982). In normal cells, CpG islands in gene promoter regions are usually unmethylated and DNA repetitive elements are heavily methylated. However, alterations of DNA methylation are commonly observed in cancer. Global hypomethylation of DNA as well as hypermethylation in the regulatory region of tumor-suppressor genes have been found in many types of human tumors (Esteller, 2008; Feinberg and Vogelstein, 1983; Gama-Sosa et al., 1983).; Although it is not clear how this aberrant DNA methylation occurs in cancer, potential mechanisms have been proposed. First, aberrant expression of DNA methyltransferases which transfer a methyl group to cytosines could play a role on aberrant DNA methylation. Second, DNA methylation changes can be influenced by the modifications in histone structure that are commonly disrupted in cancer cells (Fraga et al., 2005b; Seligson et al., 2005). Third, environmental factors which are associated with tumorigenesis could affect aberrant DNA methylation in cancer.; In order to reverse aberrant epigenetic alterations, epigenetic therapies including DNA methylation inhibitors and histone deacethylases inhibitors have been used to treat cancer. In addtion an optimal combination regimen by combining DNA methylation inhibitors with other drugs is under clinical investigation (Yoo and Jones, 2006).; This thesis examined DNA methylation changes in cancer, a possible mechanism of DNA methylation changes, and possible ways to therapeutically reverse DNA methylation changes. |
| Keyword | DNA methylation; DNA repetitive elements; cancer; DNA methyltransferase; epigenetic therapy; DNA methylation inhibitor |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1510 |
| Rights | Choi, Si Ho |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Choi-2264 |
| Archival file | uscthesesreloadpub_Volume40/etd-Choi-2264.pdf |
Description
| Title | Page 1 |
| Full text | STUDIES ON THE ALTERATION OF DNA METHYLATION IN CANCER by Si Ho Choi A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (MOLECULAR PHARMACOLOGY AND TOXICOLOGY) August 2008 Copyright 2008 Si Ho Choi |
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