Coordinated upregulation of peroxiredoxins in breast cancer

Peroxiredoxins (Prdxs) are a group of thiol-specific antioxidant proteins that are involved in many cellular processes, including growth, proliferation, differentiation, and the stress response. The family includes six proteins in humans, which show differences in substrate specificity, tissue expression, and cellar localization and distribution. Cancer cells commonly exhibit aberrantly regulated expression of antioxidants, which can support cancer cell survival in the face of elevated levels of reactive oxygen species. Breast cancers exhibit significantly elevated Prdx levels of Prdx. We previously reported overexpression of many Prdx proteins in the MCF-7 breast cancer line, and further demonstrated their importance in cell survival and doxorubicin-resistance in this line. To further investigate the misregulation of these proteins in human breast cancer, we compared Prdx levels between breast tumor and adjacent normal breast tissue from 20 breast cancer patients. We showed that most patients exhibited elevated levels of several Prdx proteins in the tumor tissue. We have gone on to analyze the promoters of these genes in an effort to identify potential mechanisms of coordinate regulation, as well as downstream targets that may mediate their role in cell survival. Together, we feel that this family of proteins may be useful biomarkers, and also targets, in breast cancer biology.