All ETDs from UAB

Advisory Committee Chair

Trygve O Tollefsbol

Advisory Committee Members

Molly S Bray

James A Coker

Document Type

Thesis

Date of Award

2012

Degree Name by School

Master of Science (MS) College of Arts and Sciences

Abstract

Neoplastic reprogramming generates cancerous cells from normal derivatives, enabling researchers to create a model of the early stages of oncogenesis and analyze molecular changes in real-time. Aberrations in DNA methylation are considered a major mechanism contributing to the acquisition and maintenance of a cancerous phenotype; however, little research exists regarding gene-specific changes in DNA methylation during the transition from a normal to neoplastic cell. Human mammary epithelial cells (HMECs) underwent neoplastic transformation through the addition of three defined genetic elements to generate one line of semi-transformed, pre-malignant cells (SHMECs) and two separate lines of fully transformed, malignant cells (THMECs). We used an Illumina Infinium HumanMethylation27 BeadChip to interrogate 27,578 CpG loci and identify genes that exhibited differential methylation over three consecutive time points during breast tumorigenesis. We found 805 CpG loci exhibiting a single DNA methylation change from SHMEC to THMECs at 40 days (THMEC-40d). These genes were enriched for biological functions associated with cellular growth and proliferation. In contrast, 196 CpG sites were differentially methylated between THMEC-40d and THMEC-80d and were associated with major developmental processes. The data generated provide novel insight into the both the timing and possible role of specific DNA methylation changes throughout the initiation and progression of breast oncogenesis. However, additional studies are necessary to fully explore how these specific DNA methylation alterations, in addition to other epigenetic aberrations, mechanistically contribute to differential gene and protein expression, enabling the development of breast cancer.

Share

COinS