Differential gene expression in normal and transformed human mammary epithelial cells in response to oxidative stress.

TitleDifferential gene expression in normal and transformed human mammary epithelial cells in response to oxidative stress.
Publication TypeJournal Article
Year of Publication2011
AuthorsCortes DF, Sha W, Hower V, Blekherman G, Laubenbacher R, Akman S, Torti SV, Shulaev V
JournalFree Radic Biol Med
Volume50
Issue11
Pagination1565-74
Date Published2011 Jun 01
ISSN1873-4596
KeywordsBreast Neoplasms, Carcinoma, Cell Line, Transformed, Cell Transformation, Neoplastic, Female, Gene Expression Profiling, Glucose Oxidase, Humans, Mammary Glands, Human, Microarray Analysis, Oxidative Stress, Reactive Oxygen Species
Abstract

<p>Oxidative stress plays a key role in breast carcinogenesis. To investigate whether normal and malignant breast epithelial cells differ in their responses to oxidative stress, we examined the global gene expression profiles of three cell types, representing cancer progression from a normal to a malignant stage, under oxidative stress. Normal human mammary epithelial cells (HMECs), an immortalized cell line (HMLER-1), and a tumorigenic cell line (HMLER-5) were exposed to increased levels of reactive oxygen species (ROS) by treatment with glucose oxidase. Functional analysis of the metabolic pathways enriched with differentially expressed genes demonstrated that normal and malignant breast epithelial cells diverge substantially in their response to oxidative stress. Whereas normal cells exhibit the up-regulation of antioxidant mechanisms, cancer cells are unresponsive to the ROS insult. However, the gene expression response of normal HMECs under oxidative stress is comparable to that of the malignant cells under normal conditions, indicating that altered redox status is persistent in breast cancer cells, which makes them resistant to increased generation of ROS. We discuss some of the possible adaptation mechanisms of breast cancer cells under persistent oxidative stress that differentiate them from normal mammary epithelial cells as regards the response to acute oxidative stress.</p>

DOI10.1016/j.freeradbiomed.2011.03.002
Alternate JournalFree Radic. Biol. Med.
PubMed ID21397008
PubMed Central IDPMC3119600
Grant ListR01 CA120170-02 / CA / NCI NIH HHS / United States
T32 CA079448 / CA / NCI NIH HHS / United States
R01 CA120170 / CA / NCI NIH HHS / United States
R01 CA120170-03 / CA / NCI NIH HHS / United States
R01CA120170 / CA / NCI NIH HHS / United States
T32 CA079448-05S1 / CA / NCI NIH HHS / United States
R01 CA120170-01A2 / CA / NCI NIH HHS / United States