Induction of Peroxiredoxins in Breast Cancer
Cancer cells possess elevated levels of reactive oxygen species (ROS) that can enhance genomic instability and alter redox signaling. Aberrant antioxidant expression has also been recognized in many cancers, suggesting an adaptive response to the cancerous state. Breast cancers express significantly elevated levels of Peroxiredoxins (Prdxs), a family of thiol-specific antioxidant proteins involved in regulating cell growth and proliferation in many cell types. We previously reported overexpression of many Prdx proteins in the MCF-7 breast cancer line, as well as their importance in doxorubicin-resistance in this line. In the present study, we analyzed Prdx levels in several human breast tumor samples, and further investigated possible mechanisms of Prdx regulation in MCF-7 cells. Comparison of breast tumor and adjacent normal breast tissue from almost 20 patients showed that most patients exhibited elevated levels of several Prdx proteins in the tumor tissue. Sequence analysis revealed potential binding sites for NF-κB, Nrf2, and AP-1 in several peroxiredoxin promoters. We found high levels of NF-κB in MCF-7 cells, as compared to normal breast epithelial cells. We further showed that a chemo-resistant MCF-7 culture generated from 14 days of doxorubicin treatment exhibited markedly decreased NF- κB expression. We then used both siRNA and chemical inhibition of NF-κB to examine the effect on Prdx regulation in these cells and found gene-specific effects. This investigation will help to elucidate the role of peroxiredoxins in breast cancer cell survival, and the mechanism by which these cells alter Prdx levels to avoid death and achieve chemoresistance.
The FASEB Journal
Phelan, Shelley A.; Buurma, Valerie; Freeman, Brendan; Adzenyah, Akosua; Pettit, Gregory; Heinen, Felicitas; and Muhlbauer, Jillian, "Induction of Peroxiredoxins in Breast Cancer" (2015). Biology Faculty Publications. 82.
Phelan, S., Buurma, V., Freeman, B., Adzenyah, A., Pettit, G., Heinen, F., and Muhlbauer, J. (2015). Induction of Peroxiredoxins in Breast Cancer. The FASEB Journal, 29, (1_supplement), Abstract No. LB116.