The nuclear matrix protein, NRP/B, enhances Nrf2-mediated oxidative stress responses in breast cancer cells.
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 (H(2)O(2)), 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 H(2)O(2), 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.
Seng
Seyha
S
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Avraham
Hava Karsenty
HK
Jiang
Shuxian
S
Yang
Suping
S
Sekine
Masayuki
M
Kimelman
Noam
N
Li
Huchun
H
Avraham
Shalom
S
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D014162:Transfection; D015854:Up-Regulation
D008840:Microfilament Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009479:Neuropeptides; D020030:Nitric Oxide Donors; D009687:Nuclear Proteins; C112302:ectodermal-neural cortex 1 protein; D006861:Hydrogen Peroxide