Abstract 2075: Overexpression of the peroxiredoxin family of antioxidant proteins in MCF7 breast cancer cells and investigation of possible regulatory mechanisms

Abstract

Abstract Peroxiredoxins are thiol-specific antioxidant proteins that protect cells from oxidative stress. There are six different peroxiredoxin proteins expressed in mammalian cells, and these proteins have been implicated in the regulation of cell signaling, proliferation and apoptosis. Many recent studies have found elevated peroxiredoxin levels in cancer, suggesting that cancer cells may upregulate peroxiredoxin expression as an adaptation to the cancerous state. We compared the expression of all six peroxiredoxins between MCF7 breast cancer cell line and the non-cancerous MCF-10A cell line. We found significant overexpression of five of the six peroxiredoxins (PrdxI-V) at both the mRNA and protein level. To explore possible mechanisms of peroxiredoxin upregulation, we first compared the lines for levels of reactive oxygen species (ROS) and the activity of particular kinases implicated in cancer biology. We found that MCF-7 cells express markedly higher levels of ROS, and increased activity of ERK 1/2 and JNK 1/2, as compared to MCF-10A cells. We hypothesized that elevated ROS and/or enhanced activity of these signal transduction pathways may mediate peroxiredoxin induction in these cells. MCF-7 cells were cultured under conditions of serum deprivation, ROS reduction, or kinase inhibition to examine the effects on peroxiredoxin expression. After 48 hours of serum deprivation, the expression of Prdx2 was reduced. Using NAC treatment, we inhibited ROS accumulation in MCF-7 cells and found a decrease in expression of both Prdx2 and Prdx3. Inhibition of ERK 1/2 activity by the inhibitor PD 98,059 resulted in little to no change in peroxiredoxin levels. Finally, treatment of MCF-7 cells with hydrogen peroxide led to a transient increase in Prdx1 at 4 hours, which returned to basal levels by 24 hours. Together, these data reveal overexpression of the peroxiredoxin family in MCF-7 cancer cells, and suggest that oxidative stress and redox-sensitive kinases may play a role in mediating the upregulation of particular peroxiredoxins. Studies examining the role of JNK and p38 in peroxiredoxin induction, as well as cell line differences in multimeric Prdx complexes, are currently underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2075. doi:1538-7445.AM2012-2075