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The Nuclear Matrix Protein, NRP/B, Enhances Nrf2-Mediated Oxidative Stress Responses in Breast Cancer Cells

¹ Division of Experimental Medicine, Beth Israel Deaconess Medical Center and ² Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Shalom Avraham, Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115. Phone: 617-667-0063; Fax: 617-975-5240; E-mail: savraham{at}bidmc.harvard.edu.

The transcription factor NF-E2–related factor 2 (Nrf2) translocates into the nucleus and activates phase II genes encoding detoxification enzymes and antioxidant proteins, resulting in the protection of cells from oxidative insults. However, the involvement of Nrf2-mediated oxidative stress responses in breast cancer cells is largely unknown. Notably, during our study of the Nrf2 pathway in breast cancer cells, we observed that the nuclear matrix protein NRP/B was expressed and colocalized with Nrf2 in these cells, suggesting that NRP/B is involved in Nrf2-mediated oxidative stress responses. The expression level of NRP/B was variable in different breast cancer cells and breast cancer tissues, and was found to be localized in the nucleus. NRP/B expression was increased after exposure to the oxidative stress agent, hydrogen peroxide (H₂O₂), particularly in the highly aggressive MDA-MB-231 breast cancer cells. Association of NRP/B with Nrf2 in vitro and in vivo was observed in MDA-MB-231 breast cancer cells, and this association was up-regulated upon exposure to H₂O₂, but not to sodium nitroprusside, SIN-1, and DETA-NO. NRP/B also enhanced Nrf2-mediated NAD(P)H:quinine oxidoreductase 1 promoter activity. Thus, this study reveals that NRP/B enhances oxidative stress responses in breast cancer cells via the Nrf2 pathway, identifying a novel role of nuclear matrix protein(s) in oxidative stress responses. [Cancer Res 2007;67(18):8596–604]

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