Cancer cells are characterized by elevated ROS levels, which provide these cells with a distinct survival advantage, promoting proliferation, invasion, and resistance to apoptotic stimuli. In order to maintain ROS below a critical threshold that would otherwise result in death, cancer cells have appropriately adapted their anti-oxidative machinery. Here, I studied superoxide dismutase 1 (SOD1) as a potential contributor to cancer cell survival under conditions of high oxidative stress. I determined that SOD1 is up-regulated in a majority of cancer cells in which the activity of another dismutase, MnSOD, is reduced, and found evidence to suggest that SOD1 is essential for maintaining mitochondrial integrity in these cells. Additionally, I explored a possible mechanism by which mitochondrial SOD1 increases in cancer cells, and found evidence indicating that this is due to decreased MULAN levels. Last, I tested whether blocking SOD1 activity could sensitize cancer cells to chemotherapeutic treatment, and determined that additional mechanisms must exist to compensate for SOD1 activity loss.
|Commitee:||Germain, Doris, O'Connell, Matthew, Pfleger, Cathie|
|School:||Icahn School of Medicine at Mount Sinai|
|School Location:||United States -- New York|
|Source:||MAI 52/03M(E), Masters Abstracts International|
|Subjects:||Biology, Biochemistry, Oncology|
|Keywords:||Breast cancer, Mitochondria, Oxidative stress, Superoxide dismutase|
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