Content area
Full Text
About the Authors:
Jill E. Hesse
Affiliation: Environmental Stress and Cancer Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Liwen Liu
Affiliation: NIEHS Microarray Core, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Cynthia L. Innes
Affiliation: Environmental Stress and Cancer Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Yuxia Cui
Affiliation: Environmental Stress and Cancer Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Stela S. Palii
Affiliation: Environmental Stress and Cancer Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Richard S. Paules
* E-mail: [email protected]
Affiliations Environmental Stress and Cancer Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America, NIEHS Microarray Core, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Introduction
The ataxia telangiectasia mutated (ATM) protein plays a critical role in a vast array of cellular responses including cell cycle regulation, apoptosis, and DNA damage responses. Individuals with complete deficiencies in ATM suffer from severe ataxia, immunological disorders, and have elevated risk for developing lymphoproliferative cancers [1]. In addition to complete loss of ATM functionality, it is estimated that as many as 1% of the United States population carry one mutated copy of ATM [2], [3] and are subject to the consequences of haploinsufficiency. While heterozygous carriers do not suffer from ataxia telangiectasia syndrome, they have an increased risk of developing heart disease, diabetes, and cancers, specifically breast cancer, compared to individuals with normal ATM expression levels [2], [3]. More recent epidemiological studies have shown that ATM mutations, which cause ataxia telangiectasia in the homozygous state, are also breast cancer susceptibility alleles in heterozygous carriers [4], [5], [6], [7], [8], [9], [10]. Additionally, it has been implicated that epigenetic silencing of ATM through methylation may also play a role in breast cancer susceptibility [11], [12]....